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ON 


DIABETES  MELLITUS 


AND 


GLYCOSURIA 


BY 


EMIL  KLEEN,  Ph.D.,  M.D. 


PHILADELPHIA 

P.    BLAKISTON'S    SON    &    CO. 

IOI2  Walnut  Street 
1900 


I3oo 


COPYRIGHT,   1900,  BY  P.  BLAKISTON'S  SON  &  CO. 


PRESS  OF  Wm.  F.  Fell  &  Oo^ 

1220-24  SANSOM   ST., 
PHILADELPHIA. 


PREFACE. 


Among  the  thousands  annually  visiting  Carlsbad  in  search  of 
health  the  diabetics  present  the  greatest  clinical  interest,  and  from 
my  first  years  as  a  practitioner  in  the  Bohemian  Spa  I  sought  some 
relief  from  the  monotony  and  many  other  unsatisfactory  aspects  of 
a  practice  of  this  kind  in  a  careful  study  of  the  gly  cos  uric  dystrophy 
with  its  manifold  complications. 

Early  in  the  nineties  I  conceived  the  project  of  publishing  a 
book  upon  this  subject,  hoping  thereby  to  fill  a  want  in  the  medical 
literature  of  the  day.  Others,  however,  at  about  the  same  time 
undertook  the  same  assiduous  task.  A  few  months  after  my 
reading,  early  in  1895,  a  paper  on  "Digestion,  Metabolism,  and 
Nutritive  Needs  in  Diabetes  "  before  the  Swedish  Association  of 
Physicians,*  v.  Noorden's  highly  scientific  work  on  diabetes  was 
published,  and  almost  simultaneously  with  the  appearance  of  my 
own  long-delayed  book  in  the  Swedish  language,  Naunyn's  mag- 
nificent monograph  was  welcomed  by  the  profession. 

Still,  the  more  than  kind  reception  that  has  been  accorded  this 
book  by  the  physicians  of  my  native  country  has  led  me  to  enter- 
tain the  hope  that  the  most  important  part  of  my  clinical,  experi- 
mental, and  literary  work  of  recent  years  has  not  been  entirely  in 
vain.  I  resolved  to  give  my  book  publicity  in  some  more  widely 
used  language  than  the  one  most  familiar  to  me,  and  myself,  with 
some  few  additions  and  changes,  translated  my  book  into  English. 
In  doing  this  I  derived  considerable  assistance  from  a  dear  Ameri- 
can friend.  Finally,  Dr.  Eshner,  of  Philadelphia,  has  revised  the 
manuscript  and  added  his  most  valuable  aid  to  change  my  own 


*  See  the  "  Transactions  of  the  Association  "  ("  Hygiea  ")  for  the  same  year,  and 
the  chapter  on  Metabolism  in  this  book.  In  the  latter  I  have  added  some  references  to 
the  researches  of  the  last  few  years. 

V 


VI  PREFACE. 

somewhat  deficient  English  into  good  English,  for  which  work  I 
hereby  render  my  public  thanks.  For  the  substance  and  scientific 
matter  of  this  book  I  am  myself  alone  responsible. 

I  have  treated  the  vast  subject  of  diabetes  and  glycosuria  with 
as  much  brevity  as  is  compatible  with  my  purpose  of  giving  as 
full  a  viev/  of  it  as  the  present  time  allows,  never  having  out  of 
sight  that  my  chief  aim  is  to  facilitate  for  the  general  practitioner 
the  acquisition  of  the  knowledge  of  the  glycosuric  dystrophy,  to 
which  I  have  devoted  considerable  time  and  work. 

At   the    end  of  the  book  I    give    a  Hst  of  names  of  the  chief 

authors    on    the    subject  of  diabetes  but  no   list  of  their  works, 

as  this  alone  would  fill  a  small  volume,  and  now  that  we  have  the 

"Index  Medicus "   and  the   "Catalogue,"   seems   to   me  entirely 

superfluous. 

Emil  Kleen. 
Carlsbad,  September,  1899. 


CONTENTS. 


Chapter  Page 

I.  Definition  and  History 9 

II.  Geographic  Distribution  and  Etiology 15 

III.  Glycosurias,     26 

IV.  Symptoms  and  Complications  of  Mild  and  Severe  Diabetes,    70 
V.  Diabetes  Infantilis, 157 

VI.  Diabetes  Mellitus  Following  Extirpation  of  the  Pancreas,  164 

VII.  Metabolism  and  Nutritive  Needs 169 

VIII.  Investigation  of  a  Case  of  Diabetes 236 

IX.  Treatment, 253 

Table  of  the  Commonest  Kinds  of  Food  in  Percentages  of  Pro- 
TEiD,  Fat,  and  Carbohydrate, 295 

Personal  Register, 299 

Index 307 


vu 


DIABETES   MELLITUS 


GLYCOSURIA. 


CHAPTER   I.— DEFINITION    AND    HISTORY. 

Under  the  name  diabetes  mellitus  are  included  different  pathologic 
conditions  which,  however  imperfectly  understood,  undoubtedly  in 
most  cases  affect  the  central  nervous  system,  and  which  are  charac- 
terized by  a  faulty  metabolism,  as  a  result  of  which,  under  ordinary 
diet,  there  takes  place  the  excretion  in  the  urine  of  an  abnormally 
large  amount  of  sugar. 

Thus,  diabetes  mellitus,  so  far  as  is  at  present  known,  is  not  a 
clinical  unit,  but  a  syndrome,  the  chief  and  most  constant  symptom 
of  which  is  glycosuria,  and  which  is  represented  by  very  varying 
clinical  types. 

There  are,  however,  numerous  cases  attended  with  the  excretion 
in  the  urine  of  minute  yet  distinctly  pathologic  amounts  of  sugar, 
which  cases  differ  widely  in  clinical  aspect  and  in  prognosis  from 
the  diabetic  type,  and  which  generally  are  not  included  in  the 
designation  diabetes  mellitus. 

When  the  power  of  consuming  the  ingested  and  digested  carbo- 
hydrates is  but  little  or  momentarily  impaired,  and  when  the  patho- 
logic excretion  of  sugar,  under  ordinary  mixed  diet,  only  slightly 
exceeds  the  traces  of  sugar  found  in  normal  urine,  or  is  but  transi- 
tory, the  condition  is  not  called  diabetes  mellitus,  but  simple 
glycosuria. 

When  the  excretion  of  sugar  becomes  considerable  and  more 
persistent,  but  disappears  when  the  carbohydrates  are  decreased  or 
2  9 


lO  DIABETES    MELLITUS    AND    GLYCOSURIA. 

withdrawn  from  the  food,  the  condition,  which  generally  is  accom- 
panied by  other  more  or  less  well-defined  symptoms,  constitutes 
the  mild  stage  of  diabetes. 

The  severe  stage  of  diabetes  is  characterized  by  the  occurrence 
of  glycosuria  even  when  the  carbohydrates  are  withdrawn  from 
the  food. 

We  shall  find  that  the  limits  thus  fixed  are  far  more  distinct  on 
paper  than  in  the  reality  of  cHnical  experience,  in  which  w^e  see 
represented  all  imaginable  intermediate  stages  between  the  normal 
capability  of  consuming  the  sugar  of  the  blood  and  the  greatest 
possible  deterioration  of  this  capability. 


Our  knowledge  of  diabetes  has  essentially  developed  during  the  nineteenth 
century,  but  for  many  ages  previously  something  was  known  of  it,  as  is  shown 
in  notices  occurring  here  and  there  in  ancient  works. 

The  term  diabetes  {dia^ij-Tig :  6ia,  through ;  ^alveiv,  to  go)  is  attributed  to  the 
Roman,  Celsus,  who  lived  in  the  beginning  of  the  Christian  era.  The  term 
then  probably  comprised  both  diabetes  mellitus  and  diabetes  insipidus. 

In  the  Indian  Yajur-Vedas  we  find  definite  statements  upon  this  subject, 
and  it  seems  from  these  ancient  documents,  discovered  about  a  hundred  years 
ago,  that  Susruta,  whose  existence  was  passed  in  the  native  land  of  the 
cobra,  the  Brahman,  and  the  tiger  during  the  seventh  century,  was  familiar 
with  both  the  clinical  picture  and  the  sweet  urine  of  diabetes  mellitus,  which 
probably  then,  as  now,  was  more  general  among  the  Hindus  than  among  any 
other  race. 

Europe  was  far  behind  India  in  knowledge  of  diabetes  mellitus  during  those 
times.  As  is  always  the  case,  single  instances  occur  of  correct  guesses  long 
before  science  had  acquired  the  facts.  Paracelsus  suspected  that  a  change  in 
the  blood  is  the  cause  of  the  symptoms  of  diabetes.  It  was,  however,  not  until 
as  late  as  1674  that  the  sweet  taste  of  the  urine  was  first  noticed  by  Thomas 
Willis  (1622-1675),  and  a  whole  century  more  elapsed  before  Dobson  showed 
that  this  sweetness  is  due  to  a  variety  of  sugar.  The  idea  of  the  presence  of 
sugar  in  the  blood  of  diabetics  then  began  to  gain  ground,  and  we  find  this 
opinion  general  at  the  commencement  of  the  nineteenth  century.  Rollo  and 
Cruikshank  accepted  the  existence  of  blood-sugar  in  diabetes  ;  but  Nicolas  and 
Gueudeville,  Segalas  and  Vauquelin,  as  also  Sobeiran,  tried  in  vain  definitely 
to  demonstrate  its  presence.  Wollaston  at  first  (181 1)  denied,  but  afterward 
acknowledged,  its  existence.  Maitland  and  Ambrosiani  (1835)  believed  they 
had  found  it.  McGregor  observed  fermentation  of  diabetic  blood,  and  Simons 
found  in  the  blood  of  a  diabetic  patient  after  a  hearty  meal  0.25  per  cent,  of 
sugar,  although  only  traces  had  been  present  before  the  meal. 

All  of  these  observations,  however,  concerned  diabetes  exclusively  ;  but  as 
early  as  1826  Tiedemann  and  Gmelin  deemed  sugar  a  normal  ingredient  of 
the  blood,  and  considered  that  they  had  proved  its  presence  in  dogs,  whether 


DEFINITION    AND    HISTORY,  I  I 

the  animals  were  fed  with  carbohydrates  or  with  meat.  Early  in  the  forties  this 
observation  was  confirmed  by  Magendie  and  by  Frerichs,  and  in  1845  Thom- 
son, by  fermentation,  made  (far  too  low)  a  determination  of  the  sugar  in  the 
blood  of  fowls. 

At  the  close  of  the  forties  Claude  Bernard  began  his  all-important  investi- 
gations, which  proved  successively  the  presence  of  sugar  in  the  normal  blood 
under  all  dietetic  conditions  ;  its  production  from  glycogen  in  the  liver  ;  its 
dependence  on  nervous  influences  ;  its  increase  above  the  normal  ratio  in  cases 
of  diabetes,  and  many  other  facts,  a  knowledge  of  which  is  essential  for  a 
comprehension  of  diabetes  mellitus,  and  to  which  we  shall  have  to  return  in 
the  chapter  on  Metabolism. 

The  enormous  amount  of  work  afterward  performed  in  this  field  by  others 
has,  on  the  whole,  simply  served  to  prove  the  correctness  of  Bernard's  obser- 
vations and  conclusions,  and  it  is  only  within  quite  recent  times  that  experi- 
mental pathology  has  provided  us  with  any  material  additions  to  what  that 
most  admirable  physiologist  taught  us. 

In  1848  Traube  observed  that  sugar  disappeared  from  the  urine  of  a  dia- 
betic patient  when  carbohydrates  were  withdrawn  from  his  food,  and  that  the 
same  individual  exhibited  glycosuria  at  a  later  period,  in  spite  of  this  with- 
drawal. He  thus  discovered  the  difference  between  the  mild  and  the  severe 
stage  of  diabetes,  on  which  others,  especially  Seegen,  afterward  attempted  to 
found  a  division  into  two  different  forms  of  disease. 

Toward  the  close  of  the  fifties  Briicke  and  Bence  Jones,  independently  of 
each  other,  found  small  traces  of  sugar  in  normal  urinCf  an  event  of  import- 
ance chiefly  because  it  led  to  further  investigations  for  small  amounts  of  sugar 
in  urine  and  brought  to  light  many  instances  of  slight  glycosuria,  pathologic 
though  often  unessential,  that  present  themselves  under  different  conditions. 
Our  knowledge  of  the  simple  glycosurias,  however,  has  been  chiefly  developed 
during  the  last  two  decades,  and  is  still  increasing  year  by  year. 

Gerhardt,  in  1865,  discovered  that  a  solution  of  ferric  chlorid  causes  a  wine- 
colored  reaction  with  the  urine  of  patients  suffering  from  severe  diabetes.  This 
observation  has  proved  of  immense  importance,  as  it  greatly  facilitated  the 
diagnosis  of  severe  diabetes  and  promoted  the  study  and  the  comprehension 
of  certain  pathologic  metabolic  products,  and  of  those  acid  blood-toxins  that 
essentially  invest  the  severe  stage  of  diabetes  with  its  clinical  peculiarities. 

Lavoisier  had,  in  the  latter  part  of  the  eighteenth  century,  laid  down  the 
principles  of  metabolism,  but  it  was  not  until  the  middle  of  the  present  century 
that  our  knowledge  of  this  most  important  subject  began  rapidly  to  develop 
through  the  works  of  Liebig,  G.  Lehmann,  Bidder  and  Schmidt,  Bischoff, 
Reignault  and  Reiset,  and  others.  In  1867  Pettenkofer  and  Voit — though 
they  themselves  at  first  misinterpreted  their  own  results — taught  us  that  the 
consumption  of  oxygen,  the  excretion  of  carbonic  acid,  the  production  of  heat, 
and  the  nutritive  needs  in  the  diabetic  are  governed  by  the  usual  laws,  and 
that  they  are  not  attended  with  other  deviations  from  the  normal  than  those 
that  arise  directly  from  the  loss  of  sugar  through  its  excretion  with  the  urine. 
When,  later,  Rubner  (in  the  middle  of  the  eighties)  gave  us  his  calorimetric 
tables  of  the  nutritive  value  of  different  articles  of  food,  the  conditions  were 


12  DIABETES    MELLITUS    AND    GLYCOSURIA. 

fulfilled  for  arranging  a  rational  diet  for  diabetics,  as  for  others,  and  we  have 
been  enabled  more  effectually  to  obviate  the  mistake  of  dieting  diabetics,  with 
the  one  view  in  mind  of  eliminating  hyperglycemia  and  glycosuria,  and  with 
out  due  regard  to  dietetic  possibilities  and  to  nutritive  needs. 

In  1886  von  Mering  discovered  phloridzin-glycosuria,  which  is  curiously 
characterized  by  the  excretion  of  large  amounts  of  glucose,  with  a  diminished 
quantity  of  sugar  in  the  blood.  Three  years  later  von  Mering  and  Minkowski, 
thanks  to  the  great  accuracy  of  their  mode  of  investigation,  had  the  good 
fortune  to  discover  that  severe  diabetes  can  be  produced  by  total  extirpation 
of  the  pancreas — the  one  "  artificial  "  method  at  present  known  of  bringing 
about  with  certainty  this  variety  of  diabetes.  By  reason  of  these  two  discov- 
eries, and  in  view  of  the  far-reaching  consequences  of  the  latter,  von  Mering 
must  be  considered  as  the  investigator  that,  next  to  Claude  Bernard,  has  con- 
tributed most  effectively  to  our  knowledge  of  diabetes  mellitus. 

During  the  last  few  decades  an  extensive  literature  has  accumulated,  and 
many  valuable  contributions  have  been  made  to  the  knowledge  of  this  dystro- 
phy. In  addition  to  those  already  mentioned,  a  great  number  of  authors  have 
distinguished  themselves  in  this  connection,  among  whom  I  may  name  Frerichs, 
Bouchardat,  Cantani,  Seegen,  Pavy,  Bouchard,  G.  A.  Hoffmann,  Griesinger, 
E.  Kiitz,  von  Voit,  Naunyn,  Ebstein,  Chauveau  and  Kaufmann,  Lepine, 
Weintraud  and  von  Noorden — passing  over  no  small  number  of  others  who 
have  written  more  or  less  important  works  on  the  subject. 

Diabetes  mellitus,  being  in  its  "mechanism"  a  peculiarly  mys- 
terious disease,  with  an  undiscovered,  or  at  least  not  fully  explained, 
pathologic  anatomic  basis,  has  been  made  the  subject  of  many 
theories,  at  present  amounting  to  more  than  thirty.  In  no  other 
department  has  medicine  made  such  extended  excursions  into  the 
domain  of  purely  speculative  science,  and  nowhere  has  this  led  to 
greater  liberties  with  the  imagination.  It  is  not  my  intention  in 
this  work,  which  is  designed  for  the  practitioner,  to  enter  upon  a 
consideration  of  all  of  these  thirty  theories  ;  but  in  order  to  show 
how  weak  and  uncertain  our  search  for  truth  has  been  in  this  field, 
and  how  many  different  theoretic  possibilities  present  themselves, 
I  will  cursorily  mention  the  main  currents  of  opinions  that  have 
prevailed. 

In  former  times  the  cause  of  diabetes  was  looked  for  in  those  organs  whose 
functions  show  the  most  manifest  abnormity — /.  <?.,  the  kidneys.  This  idea, 
in  all  its  naivete,  has  been  to  a  certain  degree  revived,  though  with  numerous 
modifications,  additions,  and  limitations  by  our  views  on  phloridzin-glycosuria, 
and  by  the  auxiliary  influence  on  the  excretion  of  glucose,  attributed  on  strong 
grounds  by  many  authors  to  the  kidneys. 


DEFINITION    AND    HISTORY.  1 3 

Rollo,  the  greatest  authority  on  diabetes  at  the  beginning  of  the  present 
century,  supposed  the  cause  of  the  dystrophy  to  be  a  disturbance  of  the  diges- 
tive functions,  which  resulted  in  an  excessive  resorption  of  carbohydrate. 
Similar  opinions,  however  absurd  they  may  seem  at  present,  have  been  ex- 
pressed quite  recently  by  many  authors,  and,  among  others,  by  no  less  an 
authority  than  Bouchardat  in  his  earlier  days.  The  importance  in  the  causa- 
tion of  diabetes  of  changes  in  the  pancreas  was  suspected  long  before  Lance- 
reaux  wrote  his  paper  on  this  subject,  and  before  we  knew  the  effect  of  total 
extirpation  of  the  pancreas,  and  could  assign  to  this  organ  a  rational  position 
in  the  pathogenesis  of  diabetes.  An  intuition  of  such  a  relation  was  at  the 
bottom  of  the  views  of  Bouchardat  and  others,  and  later  found  expression  in 
Popper's  idea  of  faulty  digestion,  in  consequence  of  a  defective  secretion  of 
the  pancreatic  juice  as  a  cause  of  diabetes  mellitus. 

Since  Bernard's  great  discoveries  and  his  theory  of  the  formation  of  the 
sugar  of  the  blood  in  the  liver  from  glycogen,  and  of  its  consumption  in  the 
tissues  for  the  production  of  vital  force,  two  great  schools  have  arisen,  in  each 
of  which  several  divisions  are  apparent.  One  of  these  schools  considers  the 
cause  of  hyperglycemia  and  glycosuria — i.  e.,  of  diabetes — to  be  a  ditninisked 
consumption  of  sugar  in  the  tissues.  For  the  sake  of  brevity,  we  may  be  per- 
mitted to  say  that  the  other  school  considers  the  cause  to  be  an  increased  pro- 
duction of  sugar  m  the  liver.  According  to  some  views,  this  excessive  produc- 
tion, however,  is  of  an  entirely  passive  kind,  and  is  more  correctly  expressed 
as  a  diminished  capability  of  the  organ  of  transforming  into,  and  storing  as, 
glycogen  the  sugar  conveyed  to  it  through  the  portal  vein,  so  that  a  larger 
part  of  the  sugar  reaches  the  circulation  by  the  hepatic  veins  than  can  be  stored 
in  the  muscles  as  glycogen,  or  be  consumed  by  them.  A  large  number  of 
authors  consider  this  view  corroborated  by  the  frequency  with  which  sugar 
appears  in  the  urine  in  cases  of  cirrhosis  of  the  liver,  A  positive  participation 
on  the  part  of  the  liver  may  also  be  conceived.  Claude  Bernard  and  his 
numerous  followers  believe  this  to  consist  in  increased  activity  of  a  normal 
function  pathologically  excited  by  hyperemia.  Pavy  and  Schiff  thought  the 
production  of  glucose  in  the  liver  an  entirely  pathologic  phenomenon.  In 
both  views  a  diastatic  ferment  and  a  central  nervous  influence  transmitted 
through  the  vasomotor  nerves  are  accepted.  The  latter  influence  must  be  given 
a  place  in  every  general  theory  of  diabetes. 

Those  that  have  conceived  the  idea  of  defective  consumption  of  the  sugar 
of  the  blood  have  either  accepted  the  disappearance  from  the  organism  of  a 
ferment  that  normally  should  cause  decomposition  of  glucose  into  glycerin  and 
its  aldehyd,  and  the  cessation  of  which  embarrasses  further  oxidation  (Schult- 
zen,  Schermetjewski,  Nencki  and  Sieber,  Bence  Jones),  or  have  thought  of 
defective  oxidation  in  the  lungs  (Araki),  or  have  placed  the  fault  with  the 
muscles  (Zimmer).  Since  the  theory  of  an  "  internal  secretion  "  of  the  various 
glands  of  the  body  was  adopted,  and  the  production  of  diabetes  by  total 
extirpation  of  the  pancreas  was  demonstrated,  a  large  number  of  scientists 
have  come  to  consider  the  cause  of  diabetes  to  be  the  disappearance  from,  or 
the  diminution  in,  the  blood  of  a  "glycolytic  ferment,"  present  normally,  and 
sent  into  the  blood  by  the  pancreas  for  the  combustion  of  glucose. 


14  DIABETES    MELLITUS    AND    GLYCOSURIA. 

There  are,  moreover,  a  considerable  number  of  observers  who  have  sup- 
posed that  there  takes  place  a  diminution  in,  or  a  retardation  of,  the  entire 
"  internal  respiration,"  which  goes  on  in  all  of  the  tissues, — an  opinion  which  at 
first  obtained  some  support  from  Pettenkofer  and  Voit's  experiments  on  metab- 
olism in  diabetes  by  reason  of  their  erroneous  interpretation  of  their  results 
(Cantani,  Jaccoud,  Bouchard,  Lecorche,  Naunyn,  Huppert). 

Diametrically  opposed  to  this  opinion  is  another  advocated  by  Robin,  who 
speaks  of  an  increased  metabolism,  of  a  "  suractiviie  de  la  nutrition^ 

In  this  cursory  retrospect  I  wish  to  mention  also  Ebstein's  carbonic-acid 
theory,  which,  however  ingenious,  entirely  lacks  support  in  facts.  Ebstein 
placed  reliance  on  the  incorrect  but  once  wide-spread  supposition  that  a 
diabetic  ceteris  paribus  always  consumes  less  oxygen  and  produces  less  car- 
bonic acid  than  a  healthy  individual.  The  carbonic  acid  he  supposed  to  act  as 
a  check  on  the  diastatic  (glucose  forming)  ferment,  and  also  to  render  certain 
proteids — especially  globulins — more  tenacious.  Thus,  when  the  carbonic  acid 
— in  consequence  of  a  defect  in  the  protoplasm,  with  resulting  disturbances  of 
the  "  internal  respiration  " — is  lessened  in  diabetes,  in  the  first  instance  and  in 
the  milder  stage  of  the  dystrophy,  the  carbohydrate — i.  e.,  glycogen — is  attacked 
by  the  diastatic  ferment  more  vigorously  than  under  normal  conditions.  In 
the  severe  stage  the  globulins  are  also  decomposed  more  readily,  and  an  exces- 
sive formation  of  glucose  begins  at  their  expense.  After  Schierbeck's  investi- 
gations on  the  diastatic  ferment  in  alkaline  and  acid  solutions,  Ebstein  and 
Schultze,  in  1893,  came  to  the  conclusion  that  carbonic  acid  in  alkaline  solu- 
tions aiigmeftts  the  diastatic  activity,  and  retards  it  in  neutral  solutions,  while 
even  a  very  slight  degree  of  acidity  inhibits  it  altogether.  It  is  rather  difficult 
to  understand  how  these  facts,  together  with  the  qualities  of  the  blood  under 
normal  conditions  and  in  the  presence  of  severe  diabetes,  could  be  made  to  fit 
in  with  Ebstein's  theory,  which,  moreover,  falls  to  pieces  in  the  face  of  the  fact, 
now  fully  proved,  that  the  diabetic  produces  as  much  carbonic  acid  as  a 
healthy  individual.  Ebstein's  citation,  in  support  of  his  theory,  that  Hoesslin 
found  a  sojourn  at  a  high  altitude,  which  had  been  considered  as  increasing 
the  production  of  carbonic  acid,  to  be  favorable  for  the  diabetic,  is  an  unfortu- 
nate one,  as  Hoesslin's  experience  in  this  respect,  at  the  time  his  treatise  was 
written,  was  limited  to  a  single  case.  On  such  a  foundation  not  even  a  sup- 
position should  be  hazarded  on  the  subject  of  diabetes,  and  far  more  reliable 
facts  indicate  that  residence  at  great  heights  does  not  in  any  way  counteract 
diabetes.  (See  the  following  chapter.)  The  opinion  that  a  sojourn  at  a  high 
altitude  in  rarefied  air  materially  increases  the  production  of  carbonic  acid 
(Mermod,  Marcet)  does  not  seem  to  be  borne  out  by  facts.  U.  Mosso  came  to 
the  conclusion,  a  few  years  ago,  from  investigations  conducted  on  Monte  Rosa 
and  in  rarefied  air,  that  the  quantity  of  carbonic  acid  produced  in  respiration 
under  these  conditions  at  an  altitude  of  6400  meters  differs  but  slightly  from 
that  produced  at  an  altitude  of  286  meters  (Turin). 

Of  late  years  there  have  been  advanced  in  France — where,  since  Ber- 
nard's time,  diabetes  mellitus  has  been  the  object  of  constant  study — theories 
concerning  its  pathogenesis,  in  which  the  nervous  system,  the  pancreas,  and 
the  liver  are  all  involved.     Even  if  these  theories  can  not  as  yet  be  said  to  be 


GEOGRAPHIC    DISTRIBUTION ETIOLOGY.  I  5 

more  than  hypotheses,  they  are  nevertheless  founded  on  definite  observations 
and  are  of  actual  interest.  I  shall,  therefore,  return  to  them  in  the  chapter  on 
Metabolism,  when  we  shall  see  that  the  theories  of  an  increased  production 
and  of  a  decreased  consumption  of  sugar  both  have  solid  bases,  and  that  they 
ought  not  to  be  pitted  against  each  other  as  utterly  irreconcilable.  To  the 
present  comprehension  of  special  pathogenetic  factors  in  the  dystrophic  group, 
the  future  will  assuredly  bring  many  additions  and  corrections,  and  the 
present  generation  will,  perhaps,  in  time  be  forced  to  confess  that  "  all  our 
wisdom  was  but  folly." 


CHAPTER    II.— GEOGRAPHIC    DISTRIBUTION— ETIOLOGY. 

Diabetes  mellitus  is  a  common  phenomenon  among  civilized 
humanity,*  and  is  constantly  increasing  in  {x^Q^oncy  pari  passu 
with  the  intensity  of  cultivated  life. 

Some  time  ago  I  saw  it  stated — I  believe  it  was  by  Worms — 
that  among  men  occupied  in  intellectual  pursuits  (statesmen,  learned 
men,  professional  men,  merchants)  of  an  age  between  forty  and  sixty 
no  less  than  ten  per  cent,  are  diabetics.  Most  physicians  will  be 
inclined  to  protest  against  this  figure  as  far  too  high,  as  it  is,  if  by  the 
expression  diabetic  is  meant  a  person  that  displays  a  cUnical  type 
of  diabetes.  It  would  be  nearer  the  truth  to  place  the  number  of 
diabetics  among  the  classes  named  at  one  per  cent.  On  the  other 
hand,  if  we  call  every  person  a  diabetic  that,  taking  ordinary  food, 
excretes  habitually  and  daily  an  inconsiderable  though  pathologic 
quantity  of  sugar  in  the  urine,  Worms'  figure  would  be  rather  too 
low  than  too  high.  If  samples  of  urine  be  taken  an  hour  after 
dinner  from  a  hundred  brain-workers  between  the  ages  of  forty  and 
sixty,  it  will  doubtless  be  found,  on  testing  with  Nylander's  solu- 
tion, or  with  Trommer's  test,  verified  by  the  fermentation-test,  that 
about  fifteen  of  the  hundred  samples  contain  an  amount  of  sugar 


*  In  animals  diabetes  mellitus — unless  designedly  caused  for  experimental  purposes — 
is  very  rare,  but  it  has  been  observed  in  the  ape  (Leblanc,  Beranger-Ferand),  the  horse 
(Hiibner),  and  the  dog  (Thiermesse,  Schindelka).  Slight  glycosuria  has  also  been 
noticed  in  animals. 


1 6  DIABETES    MELLITUS    AND    GLYCOSURIA. 

that  attains  to  hundredths  of  a  per  cent. — i.  e.,  are  distinctly  patho- 
logic. It  will,  however,  also  be  found  that  the  greater  part  of  the 
"patients"  in  question  consist  of  quasi-healthy,  or,  to  use  a  better 
expression,  very  slightly  affected,  persons,  who  neither  for  the 
moment  present,  nor  are  likely  in  the  future  to  present,  decided 
symptoms  of  the  clinical  type  that  we  are  accustomed  to  call 
diabetes. 

Among  the  European  and  the  American,  Aryan,  highly  civilized 
races,  the  difference  in  the  frequency  of  diabetes,  on  comparing  large 
areas,  will  not  be  found  to  be  very  great :  not  greater  than  it  may 
be  in  different  parts  of  the  same  country.  Different  conditions  of 
life — altitude,  climate,  and  state  of  culture,  even  within  very  narrow 
limits — give  rise  to  very  considerable  variations.  Thus  we  find 
that  diabetes  is  more  common  in  Malta  and  Gibraltar  than  else- 
where on  the  shores  of  the  Mediterranean,  in  Tuscany  than  in  the 
rest  of  Italy,  in  Normandy  than  in  the  other  provinces  of  France, 
in  Vermont  than  in  the  other  States  of  the  Union. 


The  statistical  figures  that  are  available  are  assuredly  far  too  low,  as  the 
diabetic  type  is  often  not  yerY  pronounced,  and  in  the  milder  form  does  not 
cause  death,  except  through  complications  which  have  no  definite  relation  to 
diabetes.  Moreover,  these  figures  have  doubtless  been  obtained  in  very  differ- 
ent ways  in  various  places,  and  allow  of  no  absolute  comparison.  On  learn- 
ing from  Saundby  that  the  number  of  deaths  annually  from  diabetes  mellitus 
per  100,000  inhabitants  is  in  London  5.88,  in  Berlin  5.04,  in  Paris  9.6,  in 
Christiania  3.9,  in  Rome  1.67,  in  Malta  13.1  (the  highest  European  figure),  we 
can  scarcely  conclude  with  certainty  that  the  correct  figure  for  Berlin  is  higher 
than  the  correct  figure  for  Rome,  for  which  latter  city  the  figure  cited  is 
assuredly  far  too  low.  In  Malta,  however,  diabetes  is  undoubtedly  very 
common. 

In  Norway,  among  10,000  deaths,  21  are  owing  to  diabetes  mellitus  (Kiaer). 

There  is  scarcely  any  doubt  that  in  large  communities  diabetes  mellitus  is 
rapidly  increasing.  According  to  Bertillon's  statistics  (cited  from  Lepine),  dia- 
betes caused  the  following  deaths  per  annum  among  100,000  Parisians : 

From  1865  to  1873,  a  total    of  2.3  From  1885  to  1886,  a  total  of  11 

"      1873  "   1877,        "  4  "      1887  "   1892,        "  12.13 

"      1878  "   1883,        "  9 

In  Copenhagen  the  mortality  from  diabetes  has  also  increased  rapidly  and 
constantly  during  the  past  few  decades.  From  i860  to  1864,  according  to 
Caroe,  there  was  but  one  death  per  62,840  inhabitants,  while  from  1890  to  1894 
there  was  one  per  12,855. 


GEOGRAPHIC    DISTRIBUTION ETIOLOGY.  1/ 

Purdy's  statistics  for  the  United  States  are  demonstrative  and  show  : 

In  1850,     72  per  10,000  deaths.  In  1870,  170  per  10,000  deaths. 

"   i860,    98    "        "  "  "  1890,  191    "        "  " 

Purdy,  undoubtedly  with  due  cause,  ascribes  the  enormous  increase  after 
i860  to  the  rapid  increase  of  prosperity,  the  luxurious  mode  of  life,  and  the 
more  arduous  struggle  for  existence  after  the  Civil  War. 


Of  all  races,  the  Hindu  is  most  susceptible  to  diabetes.  In  India 
and  Ceylon  diabetes  is  a  very  common  disease  among  the  upper 
classes, — so  common  that,  according  to  the  editor  of  the  "  Indian 
Medical  Gazette,"  almost  every  family  in  Calcutta  belonging  to 
these  classes  of  society  has  lost  one  or  more  members  by  death 
from  this  dystrophy,  while  another  author  (Bose)  estimates  the 
number  of  deaths  from  diabetes  in  Calcutta  at  lo  per  cent,  of  the 
entire  mortality  (!  ! !), — a  circumstance  that  must  be  attributed  to 
the  highly  nervous  constitution  of  the  Hindus,  their  early  marriage, 
and  excessive  sexual  life  in  general,  the  high  intellectual  cul- 
ture at  present  prevalent  in  India  among  these  classes,  their 
sedentary  mode  of  life,  and  perhaps  also  their  diet,  so  rich  in 
sugars  and  other  carbohydrates.  The  preponderance  of  male  over 
female  patients  seems  to  be  at  least  as  great  as  in  Europe.  Among 
the  Mohammedan  population  in  India  diabetes,  though  not  rare,  is 
not  nearly  so  common  as  among  the  Hindus. 

Next  to  the  Hindus  the  Jews — who  in  many  respects  occupy 
the  same  relative  position  to  Europeans  in  general  as  do  the  Hindus 
to  the  Jews — are  highest  in  the  scale  of  diabetic  frequency.  No 
specialist  in  diabetes  can  avoid  noticing  the  comparatively  large 
percentage  of  patients  among  Hebrews,  who  also  are  a  nervous 
race,  and  who  for  centuries  have  devoted  themselves  almost  exclu- 
sively to  intellectual  and  sedentary  pursuits. 

It  has  been  of  interest  to  me  to  form  some  estimate  of  the 
frequency  of  diabetes  among  the  Chinese,  who  seemed  to  me, 
during  the  few  weeks  I  spent  among  a  vast  number  of  their  race, 
to  be  a  nation  with  a  highly  developed  intellectual,  but  compara- 
tively slightly  developed  emotional,  life,  rather  difficult  of  compre- 
hension for  any  other  than  a  Chinaman.  Saundby's  statements 
seem  to  prove  that  diabetes  is  very  rare  among  Chinese  laborers. 
Graham,  who  at  Sumatra  practised  among  15,000  of  them,  discov- 


1 8  DIABETES    MELLITUS    AND    GLYCOSURIA. 

ered  but  a  single  case  during  his  seven  years'  sojourn.  In  the 
United  States,  I  have  myself,  from  various  sources  of  information, 
come  to  the  conclusion  that  the  disease  is  far  more  uncommon 
among  the  lower  classes  of  the  Chinese  than  among  the  same 
classes  of  Americans  and  Europeans.  On  the  other  hand,  Dr. 
Cantlie,  who  for  many  years  has  practised  in  Hong  Kong,  has  kindly 
informed  me  that  among  the  ricJicr  Chinese  diabetes  is  not  at  all 
uncommon,  adding  the  interesting  information  that  it  more  espe- 
cially attacks  those  that  change  from  the  usual  Chinese  diet,  with 
its  preponderance  of  rice,  to  a  more  mixed  European  diet.  I 
presume  this  observation  to  be  perfectly  correct ; — just  as  I  have 
repeatedly  found  that  in  cases  of  very  slight  glycosuria  I  can  cause 
a  larger  quantity  of  sugar  to  appear  in  the  urine  by  mixed  test- 
meals  than  by  those  that  consist  exclusively  of  carbohydrates. 

Among  the  contented  Japanese,  whose  education  has  hitherto 
been  Spartan  in  many  respects,  diabetes  is  not  common.  If,  as  is 
probable,  they  ere  long  provide  reliable  statistics,  it  will  doubt- 
less be  seen  that  with  the  nation's  wonderful  and  rapid  adop- 
tion of  European  culture,  the  frequency  of  diabetes  will  quickly 
increase. 

Among  the  Persians  diabetes  is  said  to  be  less  general  than 
among  Europeans,  and  the  same  is  stated  of  the  Turks  (Tholozan). 
Among  the  Arabs  of  the  part  of  North  Africa  under  French  sway 
the  dystrophy  is  not  rare  (Calmette  and  others). 

It  is  interesting  to  learn  that  among  the  laborers  on  the  sugar- 
plantations  of  the  Mauritius  and  British  Guiana,  where,  relatively 
speaking,  the  lower  classes  consume  an  enormous  amount  of  cane- 
sugar,  diabetes  meUitus  is  rarely  encountered  (Blair,  Saundby), 
From  Venezuela  the  same  statement  has  been  forwarded  to  me. 
Almost  all  these  laborers  are  "  colored  "  and  belong  to  those  races 
among  which  diabetes  mellitus  is  uncommon  as  a  general  rule. 
Circumstances,  however,  seem  to  indicate  that  a  strongly  saccharine 
diet  has  per  se  but  little  etiologic  influence. 

Among  all  people  beyond  the  pale  of  culture,  diabetes  is  very 
rare.  This  I  believe  to  be  the  correct  way  of  viewing  the  afore- 
mentioned immunity  among  Africans,  and  the  reason  why  so  little 
is  heard  of  diabetes  among  the  Indians  of  America,  or  among  the 
numerous  and  various  aborigines  of  AustraUa,  or  in  the  English 


GEOGRAPHIC    DISTRIBUTION ETIOLOGY.  1 9 

colonies  of  mixed  but  predominant  colored  population.  With 
greater  intellectual  exertion,  keener  emotions,  higher  nervous 
development,  more  earnest  struggle  for  existence,  more  urgent 
demands,  a  more  intense  culture,  in  fine,  we  are  bound  to  find 
more  diabetes  mellitus. 

From  what  we  have  already  learned  we  should  a  priori  be 
inclined  to  believe  diabetes  to  be  far  more  common  among  a  given 
number  of  residents  in  cities  than  among  the  same  number  of  per- 
sons in  the  country.  There  is,  therefore,  nothing  remarkable  in 
the  large  number  of  statements  that  support  such  a  supposition. 
On  the  other  hand,  it  is  an  interesting  fact  that  statistics  point,  in 
some  degree,  in  the  opposite  direction.  In  Great  Britain  there  are 
several  counties  with  a  large  urban  population  which  are  low  in  the 
scale  of  diabetes,  while  others  with  a  far  greater  rural  population 
are  high  in  the  scale.  Purdy  has  compared  the  figures  in  the 
United  States,  and  has  come  to  the  conclusion  that  in  the  North 
diabetes  is  more  general  among  the  rural  population,  and  in  the 
South  among  the  urban  population  ;  and  he  ascribes  this  difference 
to  the  better  protection  against  cold  afforded  by  the  cities  as  com- 
pared with  the  country,  which  holds  good  only  for  the  North.  In 
the  South  other  differences  determine  the  result.  These,  in  my 
opinion,  do  not,  as  Purdy  supposes,  consist  in  the  better  oxidation 
secured  through  the  country  air,  but  in  the  mode  of  hfe  of  the  inhabi- 
tants of  the  country,  which,  as  a  general  rule,  is  far  more  free  from 
nervous  influences.  Except  during  the  first  decades  of  life,  when 
diabetes  mellitus  is  very  rare,  and  attacks  fully  as  many,  or  perhaps 
more,  girls  than  boys,  this  dystrophy  is  far  more  common  among 
males  than  among  females — naturally,  in  consequence  of  the  severe 
struggle  for  existence  on  the  part  of  men,  and  their  greater  prone- 
ness  to  excesses.  The  difference  plainly  appears  in  the  second 
decade,  and  is  manifest  in  all  following  decades.  Generally,  there 
are  three  times  as  many  male  patients  as  female.  Exclusive  of  the 
ages  under  twenty,  Pavy  had  928  males  and  373  females  ;  Grube 
had  137  male  and  40  female  cases,  while  my  own  experience  shows 
nearly  three  male  to  every  female  patient. 

Diabetes  is  rare  in  childhood  and  youth,  the  greater  number  of 
the  patients  being  attacked  during  the  most  exacting  period  of  their 
life — from  forty  to  sixty  years  of  age. 


20  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Pavy's*  table  shows  : 


Age. 

< 

< 
s 

M 

< 

h 
0 

h 

Male. 

Female. 

Total. 

Under  lo,    .    . 

3 

5 

8 

0.22  per  cent. 

0.36  per  cent. 

0.58  per  cent. 

From  lo  to  20, 

35 

22 

57 

2.57        " 

0.61        " 

4.19 

"     20  to  30, 

69 

28 

97 

5.07        " 

2.05        " 

7.13       " 

"     30  to  40, 

154 

70 

224 

11.32        " 

5-14       " 

16.47        " 

"     40  to  50, 

260 

79 

339 

19. II        " 

5.80 

24.92       " 

"     50  to  60, 

281 

137 

418 

20. 66       ' ' 

10.07        " 

30.73        " 

"     60  to  70, 

i.3« 

44 

182 

10.14       " 

3-23        " 

13-37       " 

"     70  to  So, 

25 

9 

34 

1.83       " 

0.66        " 

2.49       " 

"     80  to  90, 

I 

I 

0.07       " 

0.07       " 

A  mild  and  warm  diviate  seems  to  give  rise  to  less  diabetes  than 
a  severe  and  cold  one.  High  altitude  tends  to  increase  the  fre- 
quency of  diabetes.  The  mortality  among  diabetics  is  also  greater 
during  the  cold  than  during  the  warm  season. 

The  diabetic  patient  of  Northern  Europe  passes  the  winter  on  the  Riviera 
with  decided  advantage  to  his  health,  and  his  brother  in  misfortune  in  North 
America  derives  benefit  from  a  sojourn  in  Florida,  or  in  Southern  California, 
during  the  severe  cold  season.  Statistics  from  the  United  States  speak  strongly 
for  the  unfavorable  influence  of  rigorous  climates.  According  to  Purdy,  Ver- 
mont, with  6.3  deaths  from  diabetes  per  1000  deaths,  stands  highest  in  the  scale 
among  all  the  States.  It  is  remarkable  for  its  cold  winters,  and  a  large  part  of  the 
State  is  from  3000  to  5000  feet  above  the  level  of  the  sea.  Next  comes  Maine, 
with  4.41  deaths  per  1000,  and  having  also  a  severe  climate,  though  less  severe 
than  that  of  Vermont,  and  at  a  lower  level.  As  a  rule,  the  "  northeastern  hills 
and  plateaus  "  constitute  those  parts  of  the  United  States  that  are  most  favorable 
to  the  development  of  diabetes.  Purdy  gives  the  mortality  from  diabetes  in 
thirty  of  the  most  populous  States,  the  average  for  a// being  1.93  among  1000 
deaths.  Taking  the  figures  from  Arkansas,  Alabama,  Texas,  Louisiana, 
Georgia,  and  the  Carolinas,  I  find  an  average  of  0.84  among  1000  deaths,  while 
the  corresponding  figure  for  Connecticut,  Massachusetts,  Maine,  Vermont, 
Illinois,  Wisconsin,  Michigan,  and  Minnesota  is  3.21.  Although  I  entirely 
agree  with  Dr.  Purdy  that  cold  and  altitude  are  the  chief  climatic  features  that 


*Schmitz,  who  (1892)  had  treated  2700  diabetic  patients,  and  who  has  the  largest 
private  statistics,  furnishes  similar  figures.  I  am  unable,  at  this  moment,  to  produce  his 
latest  table.  He  practised  chiefly  at  a  health  resort,  and  his  figures  are,  therefore,  as 
will  be  easily  understood,  of  less  weight  than  Pavy's,  who  obtained  his  from  an  estab- 
lished urban  practice.  The  English  reports  of  the  Registrar-General  can  not  be  used, 
as  they  include  both  diabetes  mellitus  and  insipidus. 


GEOGRAPHIC    DISTRIBUTION ETIOLOGY.  21 

determine  high  mortality  from  diabetes,  I  can  not  escape  the  thought  that  this 
comparison  of  mine  is  only  apparently  so  very  demonstrative.  The  figures 
would  be  conclusive  but  for  the  larger  colored  population  and  less  intensity  of 
life  and  strife  in  the  Southern  States. 

Hereditary  influences  are  of  great  importance  in  the  etiology  of 
diabetes.  In  a  large  number  of  cases  it  will  be  found  on  careful 
investigation*  that  the  diabetic  patient  is  the  descendant  of  a  dia- 
betic ;  and  still  more  frequently,  the  nervous  predisposition,  which 
in  the  patient  has  found  its  expression  in  diabetes,  has,  in  preceding 
generations,  shown  itself  in  the  form  of  other  affections  with  well- 
known  changes  in  the  central  nervous  system,  in  fully  developed 
psychoneuroses,  or  in  psychopathic  manifestations  of  various 
kinds.  It  is  often  found  that  several  members  of  the  same 
family — brothers  and  sisters — are  diabetic,  sometimes  exhibiting 
different  forms  of  the  dystrophy.  Now  and  again  I  have  found 
slight  glycosuria  and  mild  and  severe  diabetes  in  members  of  the 
same  family. 

All  of  the  "  learned  " /r(?/£'i'j'/<?;/i'  provide,  comparatively  speak- 
ing, a  vast  clinical  material  for  the  specialist  in  diabetes.  Physi- 
cians especially — who  are  compelled  to  devote  themselves  to  study 
assiduously,  to  sustain  great  responsibilities,  are  disturbed  at 
night,  and  are  harrassed  by  the  suffering  and  unreasonable  public 
— are  often  victims  of  diabetes  or  exhibit  simple  glycosuria. 
Statesmen  and  politicians  are  still  more  common  subjects  of  the 
dystrophy  in  a  greater  or  less  degree.  The  position  of  the  specu- 
lator and  the  business  man  is  best  illustrated  by  the  adage  from 
Wall  Street,  New  York  :  "  When  stocks  fall,  glycosuria  rises." 
Among  the  comparatively  "  unlearned  "  occupations   it  seems  to 


*  Close  investigation,  which  in  this  connection  is  far  more  necessary  in  order  to  ob- 
tain reliable  information  than  under  ordinary  conditions,  is  not  only  trouhlesome,  but  is 
attended  with  numerous  difficulties.  Many  a  layman  considers  neither  hypochondria  nor 
the  slighter  forms  of  melancholia  as  diseases  of  the  mind,  and,  as  a  general  rule,  he  is 
not  willing  in  his  own  case  or  in  that  of  his  relatives  to  acknowledge  any  disorder  as 
such  that  has  not  been  treated  in  an  asylum.  Many  laymen  also  entirely  disregard 
Graves'  disease,  if  not  very  pronounced,  slight  attacks  of  epilepsy,  etc.  Others  con- 
sciously conceal  a  history  of  both  psychoses  and  neurotic  tendencies  in  their  own  family, 
and  feel  ill  at  ease  and  irritated  by  being  questioned  too  closely  on  those  subjects.  In 
fully  a  quarter  of  all  cases  of  diabetes  there  exists  a  direct  diabetic  hereditary  predispo- 
sition, while  a  neurotic  heredity  is  present  in  the  great  majority. 


2  2  DIABETES    MELLITUS    AND    GLYCOSURIA. 

me  that  sailors  furnish  the  largest  contingent  of  cases  of  diabetes. 
It  is  not  among  the  crews,  but  among  the  officers,  that  the  greater 
number  of  diabetic  patients  will  be  discovered.  I  must  have  seen 
a  score  of  sea-captains,  usually  affected  but  slightly,  middle-aged, 
often  corpulent,  whose  voices  and  figures  often  remind  one  of 
"  Captain  Cuttle."  The  great  responsibility,  the  disturbed  sleep 
at  night,  the  good  table,  the  drinks,  and  the  limited  exercise,  possi- 
bly also  the  low  temperature  prevailing  on  board,  all  contribute  to 
the  development  of  diabetes. 

The  presence  of  pathologic  quantities  of  sugar  in  the  urine  is 
far  more  common  among  the  higher  classes,  with  their  more  nervous, 
sedentary,  and  luxurious  mode  of  life,  than  in  the  lower  classes. 
On  the  other  hand,  a  far  greater  percentage  of  cases  of  diabetes 
occurring  among  the  last-mentioned  classes  is  of  the  severe  kind 
than  is  the  case  among  well-to-do  people.  In  making  this  state- 
ment I  am  perfectly  aware  that  the  less  serious  variety  of  diabetes 
is  more  often  overlooked  or  neglected  by  the  poor  than  by  the  rich, 
and  that  for  this  reason,  also,  far  fewer  mild  cases  are  treated  in 
the  public  hospitals  than  in  private  practice. 

At  Carlsbad,  with  a  visiting  public  consisting  almost  exclusively  of  persons 
of  some  means,  I  not  rarely  discover  a  case  of  previously  overlooked  mild 
diabetes,  and  far  more  often  cases  of  slight  glycosuria.  For  a  number  of 
years,  during  the  winter,  in  the  capacity  of  physician  in  one  of  the  dispensaries 
for  the  poor  in  Stockholm,  I  had  ample  opportunities  of  proving  how  compara- 
tively rare  glycosuria  is  among  such  patients. 

Among  occasional  causes  painful,  depressing,  or  irritating  emotions 
must  doubtless  be  placed  first.  The  patient  often — and  doubtless 
correctly — states  the  cause  of  his  disease  to  be  constant  vexation 
in  consequence  of  changes  in  external  circumstances,  grief  at  the 
loss  of  wife,  husband,  child,  etc.  In  far  rarer  cases  a  violent  fit 
of  anger  or  fright — influences  that  invariably  increase  glycosuria  in 
a  diabetic  and  at  times  engender  an  occasional  attack  in  a  healthy 
individual — may  give  rise  to  a  real,  even  severe,  form  of  diabetes. 
One  of  my  Carlsbad  patients, — long  ago  deceased, — a  brave  and 
loyal  officer  of  the  Prussian  Guards,  dated  both  his  Iron  Cross  and 
his  diabetes  from  that  fearful  time  outside  St.  Privat,  before  the 
longed-for  order  to  storm  was  given.     (See  Glycosurias.) 

Intellectual  overexertion,  and  more  especially  the  tiresome,  unin- 


GEOGRAPHIC    DISTRIBUTION ETIOLOGY.  23 

teresting  acquisition  of  sterile  facts,  also  plays  a  certain  role  in  the 
etiology  of  diabetes.  In  Sweden,  where  an  enormous  amount  of 
time  is  spent  at  the  universities  in  preparing  for  examinations, 
more  than  one  case  of  diabetes  in  early  years  has  come  under  my 
observation,  in  which  the  "corpus  delicti"  was  probably  the 
"cramming." 

Sexual  excesses,  both  natural  and  unnatural,  doubtless  are  most 
deleterious.  Here,  as  always,  we  find  that  what  in  one  person 
causes  diabetes,  in  another  causes  glycosuria,  and  the  presence  of 
small  quantities  of  sugar  in  the  urine  in  cases  of  sexual  neuras- 
thenia— especially  in  youths  that  have  practised  much  masturba- 
tion— is  not  uncommon.  Such  an  occurrence  is  sometimes  only 
transient ;  but  at  other  times  diabetes  develops  in  persons  of  middle 
age,  in  whose  case  no  other  point  of  importance  can  be  discovered 
in  the  history  than  neurasthenia  acquired  in  youth  in  the  manner 
described.  The  sudden  enormous  increase  in  the  frequency  of 
diabetes  just  about  the  fifteenth  year  of  life  and  the  first  manifesta- 
tion of  its  preponderance  among  males  as  compared  with  females 
at  this  time,  is  doubtless  owing  partly  to  the  strained  intellectual 
activity  often  entered  upon  even  at  that  early  period,  but  also  in 
part  to  masturbation,  which  is  then  so  often  practised.  Both  of 
these  causes  are  far  more  prevalent  am.ong  boys  than  among 
girls. 

Some  of  our  habitual  luxuries  that  powerfully  affect  the  nervous 
system  certainly  exercise  a  predisposing  influence  in  the  development 
of  diabetes.  This  is  principally  the  case  with  spirits  for  the  occa- 
sional effects  of  which  I  must  refer  the  reader  to  Alcoholic 
Glycosuria.  I  suspect,  however,  that  a  similar  influence  is  exerted 
by  other  habitual  poisons,  and  my  attention  has  been  called  especially 
to  the  frequency  of  glycosuria  in  patients  suffering  from  what  we 
(incorrectly)  term  "  nicotin  poisoning,"  as  a  result  of  excessive 
smoking.  This  statement  is  made  with  a  full  realization  of  the 
difficulty,  if  not  impossibility,  of  furnishing  anything  approaching 
statistical  proof  of  its  accuracy. 

A  sedentary  life  seems  to  favor  the  development  of  diabetes  mel- 
litus,  which  is  seldom  found  in  laborers,  and  is  deemed  by  many  to 
arise  from  decreased  consumption  of  the  blood-sugar  in  the 
muscles. 


24  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Profuse  consumption  of  carbohydrates,  especially  of  sugar,  is  often 
mentioned  among  the  etiologic  factors  of  diabetes.  It  stands  to 
reason  that  any  article  of  food  that  always  increases  glycosuria  in 
diabetics  will,  if  taken  in  large  quantities,  predispose  to  this  dys- 
trophy ;  nor  can  it  be  denied  that  a  large  number  of  diabetics  have 
been  fond  of  sweets.  For  my  part,  however,  I  am  inclined  to 
think  that,  on  the  whole,  it  is  too  rich  a  diet,  both  as  regards  the 
mixed  nutriment,  and  more  especially  as  regards  alcohol,  that  plays 
the  predominating  role  in  this  connection,  and  that  the  importance 
of  large  quantities  of  starch  and  sugar  has  been  exaggerated.  I 
beg  to  remind  the  reader  that  no  carbohydrate  other  than  grape- 
sugar  causes  glycosuria*  in  healthy  individuals,  and  that  laborers 
on  sugar  plantations  show  no  special  disposition  to  glycosuria  or 
diabetes;  and,  finally,  that  just  those  classes  in  China  and  Japan 
that  live  almost  exclusively  on  rice  enjoy  almost  complete  immu- 
nity from  diabetes. 

Starvation,  especially  if  continued  for  any  length  of  time,  doubt- 
less predisposes  to  diabetes.  I  refer  the  reader  to  the  glycosuria 
following  starvation,  discovered  by  Claude  Bernard,  and  more 
closely  investigated  by  Hofmeister.  (See  the  following  chapter.) 
This  form  of  glycosuria,  however,  is  generally  of  short  duration, 
although  cases  are  sometimes  encountered  in  practice  in  which 
insufficiency  of  food  seems  to  be  the  immediate  cause  of  severe 
diabetes. 

Some  time  ago  I  attended  a  girl,  eleven  years  of  age,  in  whose  case  a  care- 
ful investigation  failed  to  reveal  any  other  etiologic  factor  than  insufficiency  of 
food.  For  two  months  the  child  had  been  visiting  some  very  poor  relatives, 
and  during  that  time  had  been  constantly  underfed.  On  her  return,  when  she 
resumed  her  usual  diet,  severe  diabetes  set  in.     (See  case,  chapter  v.) 

Exposure  to  cold,  if  severe  or  often  repeated,  is  universally  con- 
sidered one  of  the  causes  of  diabetes. 

Trauma  now  and  then  may  undoubtedly  cause  diabetes,  which 
sometimes  follows  immediately,  but  sometimes  not  until  months 
have  elapsed  after  the  accident.  The  development  of  diabetes 
under  these  circumstances  is  more  likely  to  follow  trauma  of  the 

*The  glycosurias  of  the  Trappists  who  make  their  liqueur  (Charcot);  of  the  German 
students  who  consume  large  quantities  of  ale  (Kratschmer);  or  of  Swedish  students  who 
drink  arrack  and  sugar  or  Swedish  punch,  are  examples  of  alcoholic  glycosurias. 


GEOGRAPHIC    DISTRIBUTION ETIOLOGY.  2$ 

head ;  Griesinger  was  the  first  to  call  attention  to  the  fact  that 
contusions  of  various  parts  of  the  body,  however  distant  from  the 
nervous  centers,  may  lead  to  a  similar  result.  Nevertheless,  only 
an  exceedingly  small  percentage  of  traumata  give  rise  to  diabetes, 
and  such  accidents,  though  common,  do  not  act  as  a  cause  in  more 
than  about  one  per  cent,  of  all  cases  of  diabetes  in  adults.  Among 
nearly  200  of  my  own  cases  of  diabetes  in  which  the  etiology  has 
been  carefully  investigated,  I  find  only  two  cases  in  which  I  con- 
sider trauma  the  cause  with  practical  certainty.  Among  diabetic 
children,  however,  the  percentage  is  larger. 

Finally,  sunstroke  is,  in  rare  cases,  mentioned  as  a  plausible  cause 
of  glycosuria  or  diabetes. 

There  are  two  dystrophies  that  have  some,  though  as  yet  un- 
explained, connection  with  diabetes  mellitus,  and  which  undoubtedly 
constitute  a  predisposition  to  it — viz.,  obesity  -dXid.  gout. 

All  three  of  these  dystrophies  are  not  rarely  present  in  the  same 
family,  and  sometimes  even  in  the  same  individual. 

For  other  pathogenetic  points  I  must  refer  to  the  next  chapter. 
All  the  evidence  seems  to  indicate  that  whatever  may,  as  a  tran- 
sient or  less  profound  influence,  cause  glycosuria,  may,  as  a  more 
persistent  or  more  profound  influence,  cause  diabetes  in  a  mild  or 
in  a  severe  degree. 

Diabetes,  like  all  other  dystrophies,  is  sometimes  found  in  hus- 
band and  wife,  and  Schmitz  conceived  the  original,  but  not  well- 
founded,  idea  that  this  may  be  the  result  of  direct  diabetic  infection. 
I  have  myself  seen  several  such  instances  in  practice,  just  as  I  have 
seen  married  couples  suffer  from  gout  and  adiposity,  and  I  have 
always  favored  other  explanations,  too  evident  to  any  one  to  detain 
us  further,  which  seem  more  rational  than  the  theory  of  a  diabetic 
infection.  Tessier,  however,  has  written  a  thesis  in  which  this  asso- 
ciation receives  further  consideration. 


26  DIABETES    MELLITUS    AND    GLYCOSURIA. 


CHAPTER   III.— GLYCOSURIAS. 

Since  Briicke  and  Bence  Jones  found  a  reducing  and  fermenting 
substance  in  normal  urine,  the  presence  of  minute  quantities  of  sugar 
in  the  urine  of  healthy  persons,  and  its  possible  amount  within  physi- 
ologic limits,  have  been  much  discussed.  As  representatives  of 
the  extreme  views  on  this  subject  I  may  mention,  on  the  one  hand, 
Seegen,  who,  particularly  in  the  beginning  of  his  career,  attributed 
vast  pathologic  significance  to  the  slightest  trace  of  sugar  in  the 
urine ;  and,  on  the  other  hand,  we  have  Kiihne,  who  considered 
O.I  per  cent.,  and  Roos,  who  even  mentioned  0.3  per  cent.,  as 
possible  under  normal  conditions.  Breul  has  recently  estimated 
the  amount  of  sugar  in  normal  urine  as  varying  between  0.04  and 
0.2  per  cent.  The  larger  amount  is  reached  especially,  he  thinks, 
with  a  small  expenditure  of  heat,  high  surrounding  temperature, 
and  bodily  rest. 

From  the  researches  of  Abeles,  Wedenski,  Schilders,  Moritz,  and 
Baisch,  and  a  large  number  of  my  own  investigations,  I  have  come 
to  the  conclusion  that  there  is  a  trace  of  glucose  in  normal  urine, 
and  that  the  amount  in  twenty-four  hours  scarcely  exceeds  a 
thousandth  of  i  per  cent.  Some  slight  or  occasional  increase 
beyond  this  may  often  occur  without  noteworthy  significance,  but 
as  soon  as  we  reach  hundredths  or  tenths  of  a  per  cent,  we  are  within 
pathologic  limits.  The  finding  by  Worm-Miiller  of  sugar  in  18  and 
by  Nylander  in  14  samples  of  urine  from  100  "  healthy  "  individuals 
by  their  tests,  of  which  neither  yields  a  reaction  in  the  presence  of 
less  than  a  hundredth  of  a  per  cent.  ;  and  a  similar  experience  on 
the  part  of  Breul  with  Fischer's  test,  are  for  me  evidences  of  the 
great  commonness  of  slight  but  pathologic  glycosuria,  and  I  have 
always  observed  tnat  such  individuals,  though  they  can  not  be  pro- 
nounced diabetics,  are  not  perfectly  healthy,  but  will  be  found  to 
suffer  from  nervous  or  gouty  or  other  disorders. 

As  experimental  pathology  has  of  late  proved  that  various 
operations,  especially  on  the  nervous  system,  cause  excretion  of 
sugar,  so  also  has  clinical  experience  shown  that  glucose  may 
occur,  over  and  above  the  normal  traces,  under  several  pathologic, 
but  otherwise  entirely  dissimilar,  conditions,  some  of  which  are  of 


GLYCOSURIAS.  2/ 

a  passing  nature,  though  others  may  last  for  the  greater  part  of 
a  long  life.  We  should  never  disregard  or  pass  over  without 
thorough  investigation  a  measurable  quantity  of  glucose  in  the 
urine  ;  but  we  must  avoid  attaching  too  great  an  importance  to  the 
excretion  of  minute  amounts,  even  if  repeated  daily,  and  pro- 
nouncing at  once  as  diabetic  every  person  whose  urine  yields  a 
positive  reaction  to  tests  for  grape-sugar.  It  is  now  impossible  to 
change  the  clinical  and  prognostic  idea  that  physicians  and  laymen 
alike  for  centuries  have  attached  to  the  expression  diabetes  melli- 
tus.  A  person  that,  upon  an  abundant  mixed  food,  excretes,  e.  g., 
0.5  gram  of  glucose  in  the  twenty -four  hours  is  no  diabetic  in  this 
sense,  even  if  this  insignificant  excretion  is  maintained  for  years. 
Such  manifestations  occur  more  especially,  and  in  large  numbers, 
among  neurasthenic  and  among  gouty  patients.  The  division  of 
all  the  various  forms  and  conditions  attended  with  pathologic  excre- 
tion of  glucose  into  simple  glycosuria,  mild  and  severe  diabetes  is 
the  one  that  best  corresponds  to  the  clinical  reality,  and  the  only 
one  that  seems  to  me  possible  at  the  present  day. 

A  rational  classification  of  the  different  forms  of  simple  glyco- 
suria is  at  present  entirely  impossible,  owing  to  our  defective  knowl- 
edge of  pathogenetic  details  ;  we  must,  for  the  time  being,  content 
ourselves  with  a  table.  At  the  head  of  the  list  we  place  alimentary 
glycosuria,  common  alike  to  healthy  and  to  diabetic  persons  after 
the  ingestion  of  large  quantities  of  grape-sugar.  Next  come  the 
glycosurias  that  arise  from  disorders  in  those  organs  that,  even 
though  the  modus  operandi  is  not  as  yet  completely  understood, 
undoubtedly  influence  directly  the  metabolism  of  the  carbohy- 
drates :  the  nervous  system,  the  pancreas,  and  the  liver.  The 
7ievvous  glycosurias  may  be  subdivided  into  organic  and  functional, 
with  known  or  unknown  lesions  of  the  nervous  system.  (The 
former  include  a  number  of  experimental  glycosurias.)  Lesions  in 
the  pancreas  may  give  rise  to  simple  glycosurias,  or  to  mild  or 
severe  diabetes  ;  but  the  pancreatic  glycosurias  are  treated  of  at 
length  in  a  special  chapter,  and  are  therefore  omitted  from  further 
consideration  here.  There  are  also  hepatic  glycosurias,  but  these 
are  only  known  imperfectly  from  experimental  and  clinical  obser- 
vations. 

Among   toxic  glycosurias,    that    due    to    alcohol   possesses    the 


28  DIABETES    MELLITUS    AND    GLYCOSURIA. 

greatest  practical  importance  ;  and  those  due  to  pliloriddn  and  to 
carbon  nionoxid,  the  greatest  theoretic  interest.  Among  glycos7irias 
from  infectioti,  those  that  complicate  malaria  or  influenza  are  the 
most  common.  In  this  category  we  include  also  that  excretion  of 
sugar  in  the  urine  that  has  been  observed  in  association  with  puru- 
lent processes.  Among  "concomitant"  glycosurias,  special  stress 
should  be  laid  on  those  that  occur  in  conjunction  with  obesity,  gout, 
and  diabetes  insipidus,  all  of  which  are  allied  to  diabetes  mellitus. 
Glycosuria  sometimes  arises,  further,  from  cold,  from  starvation,  and 
from  fatigue.  It  may  occur,  also,  in  the  fetus,  and  it  may  be  of 
puerperal  origin.  Finally,  pathologic  quantities  of  sugar  are  often 
observed  in  the  urine  in  senility  and  in  cachectic  states.  Of  late 
years  much  has  been  written  of  renal  glycosuria,  and  there  seems 
to  be  no  doubt  that  the  kidneys  have  some  influence  on  the  excre- 
tion of  sugar.  The  glycosuria  from  phloridzin  may  also  be 
included  in  the  renal  variety.  With  regard  to  the  glycosuria  that 
is  attributed  to  cardiac  disease  (Reynoso,  Neumann),  our  knowledge 
seems  at  present  to  be  too  scanty  to  permit  of  any  conclusion. 

Of  all  these  forms  of  glycosuria  the  acute  alcoholic  and  the 
chronic  functional  neurotic,  and  the  equally  chronic  gouty,  are 
the  most  common,  occurring  much  oftener  than  all  the  others 
together. 

One  attribute  is  common  to  all  nondiabetic  glycosurias  with  the 
exception  of  the  one  caused  by  phloridzin  :  viz.,  the  excretion  of 
sugar  in  varying,  though  never  considerable,  amount.  The  gly- 
cosurias are,  so  far  as  measurable  quantities  are.  concerned,  transi- 
tory in  some  sense.  Thus,  after  the  ingestion  of  a  large  amount 
of  glucose,  after  intoxication,  cold,  starvation,  fatigue,  or  violent 
emotion,  the  sugar  appears  in  the  urine  only  for  a  short  while, — 
sometimes  only  for  hours, — and  then  generally  disappears,  never  to 
return.  After  infections,  childbirth,  etc.,  sugar  may  appear  in  the 
urine  for  a  number  of  days,  but  rarely  persists  for  more  than  a 
few  weeks.  In  cases  of  neurasthenia,  gout,  and  obesity,  or  in 
senility  and  other  more  permanent  states,  the  glycosuria  may  reach 
measurable  amounts  for  only  a  short  while  some  time  after  meals, 
and  it  may  remain  stationary  at  this  point  for  years  ;  though  every 
now  and  then,  as  sometimes  happens  also  after  transitory  influences, 
it  may  be  converted  into  true  diabetes. 


GLYCOSURIAS.  29 

Glycosuria  is  in  most  cases  an  immediate  effect  of  hypergly- 
cemia, or  the  presence  of  an  increased  amount  of  sugar  in  the 
blood,  though  the  relation  between  the  blood-sugar  and  the  urine- 
sugar  is  not  a  perfectly  fixed  one,  and  some  influence  on  the  part 
of  the  kidneys  must  be  accepted.  (See  below.)  Claude  Bernard 
found  that  the  dog,  whose  blood  contains  normally  about  from 
o.  10  to  0.15  per  cent,  of  sugar,  begins  to  exhibit  glycosuria  when 
the  hyperglycemia  reaches  from  0.25  to  0.30  percent.  I  accept 
the  normal  glycemia  in  man  as  vaiying  between  o.  10  and  0.15  per 
cent.,  and  from  the  figures  of  Seegen  and  others  it  must  be  con- 
cluded that  glycosuria  may  appear  when  the  amount  of  sugar  in 
the  blood  is  only  slightly  above  the  last-named  figures  (even  below 
0.20  per  cent.). 

Hyperglycemia  is,  however,  not  a  necessary  prerequisite  for  gly- 
cosuria. The  quantity  of  sugar  in  the  blood  is  abnormally  low  in 
phloridzin-glycosuria.  The  same  condition  exists,  according  to 
Dastre,  in  the  glycosuria  due  to  slozv  asphyxiation.  Hibernating 
animals,  according  to  some  observations,  exhibit  glycosuria ; 
although  the  quantity  of  sugar  in  the  blood  diminishes  during 
hibernation,  and  increases  rapidly  as  the  animals  resume  their 
accustomed  activity  (Claude  Bernard),  and  their  glycosuria  disap- 
pears. According  to  Bernard,  the  amniotic  fluid  of  the  fetus  (its 
urine)  often  contains  sugar.  The  normal  glycemia  of  the  fetus  is, 
so  far  as  I  know,  not  yet  satisfactorily  determined,  but  it  seems  to 
me  possible  that  we  might  have  here  another  example  of  hypo- 
glycemia with  glycosuria.* 

Aliineiitary  glycosuria  occurs  normally  after  the  ingestion  of 
large  quantities  of  glucose,  and  it  is  of  great  importance  to  remem- 
ber that,  so  far  as  human  beings  are  concerned,  this  is  the  sole 
physiologic  variety  of  purely  "alimentary"  glycosuria — which  ex- 
pression is  often  incorrectly  applied.  The  largest  possible  quan- 
tities of  ingested  starch  cause  no  glycosuria  in  healthy  persons. 
After  the  ingestion  of  large  quantities  of  sugars  other  than  glucose 

*0n  the  other  hand,  Naunyn  mentions  cases  in  which  the  amniotic  fluid  of  the  fetus 
contained  no  sugar,  even  when  the  mother  suffered  from  diabetes;  this  fluid,  in  other 
cases  of  diabetes,  may  contain  quite  a  considerable  quantity  of  glucose  (0.7  per  cent., 
Husband). 


30  DIABETES    MELLITUS    AND    GLYCOSURIA. 

the  urine  will  be  found  to  contain  normally  only  a  small  part  of 
the  same  kind  of  sugar  ;  we  thus  may  have  a  physiologic  saccha- 
rosuria,  a  lactosuria,  laevulosuria,  etc.  (see  below). 

Alimentary  glycosuria  evidently  is  caused  by  failure  on  the  part 
of  the  liver  to  transform  into  glycogen  very  large  quantities  of  glu- 
cose entering  into  that  organ  through  the  portal  vein.  The  excess 
that  is  not  transformed  or  is  not  stored  or  consumed  in  other 
organs  (muscles)  passes  into  the  urine. 

Numerous  experiments  of  my  own  with  glucose  in  normal  and 
diabetic  individuals  have  confirmed  essentially  several  facts  pre- 
viously observed  by  Worm-Miiller,  Kiilz,  and  others,  and  have 
taught  me  :  (i)  That  normal  individuals  can  take,  some  hours  after 
a  light  breakfast,  and  before  the  second  meal  of  the  day,  generally 
lOO,  often  200,  grams  of  glucose  without  excreting  a  measurable 
amount  in  the  urine.  The  maximum  average  amount  that  can  be 
taken  under  such  circumstances  is  probably  below  150  grams  of 
glucose.  (2)  That  this  maximum  amount — or,  in  other  words,  the 
limit  of  assimilation  (Hofmeister) — varies  vastly,  even  in  normal  in- 
dividuals, under  different,  and  sometimes  even  under  apparently 
similar,  conditions.  (3)  That  the  capacity  for  taking  glucose  with- 
out the  development  of  glycosuria  is  often  greater  earlier  than  later 
in  the  day.  (4)  That  a  healthy  individual  excretes,  as  a  rule,  far 
less  after  the  same  amount  of  glucose  than  does  a  diabetic  ;  but  (5) 
that  a  diabetic  in  the  mild  stage  of  the  disease  may,  by  prolonged 
abstinence  from  carbohydrates  for  the  time  being,  attain  an  equally 
high  power  of  assimilation  as  a  normal  individual ;  and  (6)  that, 
consequently,  a  simple  ingestion  of  glucose  can  not,  for  more  than 
the  time  being,  determine  the  limit  of  assimilation,  and  can  not 
always  establish  the  absence  or  presence  of  diabetes. 

Under  organic  nervous  glycosuria  are  included  those  cases  of 
slight  excretion  of  sugar  in  the  urine  that  occur  in  conjunction  with 
known  lesions  of  the  cerebrospinal  and  sympathetic  nervous  system. 
Experimental  pathology  has  evolved  some  valuable  contributions 
to  our  knowledge  of  central  action  in  this  connection  ;  but  this 
knowledge,    however,    is    very    imperfect.*       Clinical    experience 

*The  technical  difficulties  in  the  way  of  full  and  exhaustive  investigation  are  scarcely 
to  be  overcome.     Kahler's  experiments,  which,  unfortunately,  only  concerned  polyuria, 


GLYCOSURIAS.  3 1 

throws  but  a  faint  light  on  the  subject,  which  is  somewhat  increased 
by  pathologic  anatomy,     (See  below.) 

Though  isolated  observations  as  to  the  connection  between  cer- 
tain lesions  of  the  nervous  system  and  glycosuria  (or  diabetes)  had 
previously  been  made,  it  was  Claude  Bernard  who,  in  1849,  ^^^t 
demonstrated  this  relation  by  his  celebrated  "piqiire"  in  the  floor 
of  the  fourth  ventricle  between  the  centers  of  the  pneumogastric  and 
acoustic  nerves.  This  lesion  causes  a  transitory  hyperglycemia, 
coupled  with  polyuria,  and  the  presence  in  the  urine  of  glucose  to 
the  amount  of  several  parts  to  the  hundred  for  from  five  to  six  hours 
in  the  rabbit  and  about  forty-eight  hours  in  the  dog.*  Puncture  a 
little  higher,  in  a  frontal  direction,  causes  albuminuria,  while  another 
somewhat  lower  causes  simple  polyuria.  Bernard  and  many  others 
have  considered  these  phenomena  symptoms  of  irritation,  not  of 
paralysis.  As  irritation  of  the  chorda  tympani  causes  increased 
functional  activity  (and  hyperemia)  of  the  submaxillary  gland 
through  the  influence  of  sympathetic  fibers,  which  preside  over  the 
vessels  and  lead  to  their  distention,  so  is  a  vasomotor  center  in  the 
brain  irritated  by  Bernard's  puncture.  The  stimulation  is  then 
transmitted  through  the  upper  part  of  the  spine,  and  afterward 
through  the  splanchnic  nerves  to  the  vessels  of  the  abdominal 
organs  in  which  hyperemia  plainly  manifests  itself  By  the  in- 
creased flow  of  blood  to  the  liver  its  glycogen  is  attacked  more  act- 
ively than  usual  by  the  diastatic  ferment  in  the  blood,  and  the  pro- 
duction of  sugar  is  increased,  according  to  Claude  Bernard.  The 
great  physiologist  undertook  the  experiment  for  the  purpose  of  irri- 
tating the  center  of  the  pneumogastric  nerve,  and  expected  glyco- 
suria from  this  excitation.  He  discovered,  however,  that  glycosuria 
appeared  after  the  puncture  even  if  both  pneumogastric  nerves  were 

seem  to  have  given  technically  the  best  results.  He  injected  a  concentrated  solution  of  silver 
nitrate  through  a  fine  cannula,  and  thereby  caused  circumscribed  destruction  in  different 
parts  of  the  brain  of  the  rabbit.  Lesions  of  Eckhard's  "  lobus  hydruricus  et  diabeticus  " 
caused  transitory  and  inconstant  polyuria,  which  also  resulted  from  a  lesion  of  Deiter's 
nucleus  and  adjacent  parts  of  the  crura  cerebelli.  A  lesion  of  the  acoustic  tubercle 
and  acoustic  stride  caused  polyuria  within  forty-eight  hours.  Although  these  results 
hold  good  for  rabbits,  they  can  not  be  applied  without  further  experiment  to  other 
animals.      Kahler  favored  the  theory  of  stimulation. 

*  Bernard's  puncture  also  caused  glycosuria  in  pigeons  (Bernard)  and  in  frogs  (Schiff, 
Kiihne). 


32  DIABETES    MELLITUS    AND    GLYCOSURIA. 

cut ;  that  no  glycosuria  followed  irritation  of  the  peripheral  stump  ; 
that  glycosuria  may  be  caused  by  reflex  action,  if  the  central  stump 
is  irritated,  but  that  no  glycosuria  follows  the  puncture  if  previously 
both  splanchnic  nerves  are  cut  or  if  the  pancreas  and  the  liver  are 
separated  from  the  nervous  system.  The  puncture  is  now  known 
to  have  the  usual  effect  even  if  the  pancreas  is  extirpated,  and  then 
increases  the  hyperglycemia  (Kaufmann)  and  the  glycosuria 
(Hedon),  but  it  does  not  have  that  effect  if  the  celiac  plexus  is 
extirpated  (Schiff).  After  the  glycosuria  is  over,  the  glycogen  of 
the  liver  has  mostly  disappeared.  If  this  has  been  previously  re- 
moved by  starvation,  no  glycosuria  follows  the  puncture.  If  a 
certain  quantity  of  glucose  is  injected  into  the  mesenteric  veins  of 
an  animal  that  has  lost  its  glycogen  through  starvation,  a  slight 
glycosuria  follows.  A  much  more  pronounced  glycosuria  follows, 
under  otherwise  the  same  circumstances,  if  the  injection  is  preceded 
by  Bernard's  puncture  (Naunyn),  and  it  is  thus  evident  that  the 
capacity  of  the  hver  for  storing  glucose  as  glycogen  is  diminished 
by  the  puncture.  Though  the  glycosuria  following  Bernard's 
puncture  is  transitory,  and  not  very  considerable,  postmortem 
observations  (see  below)  indicate  that  permanent  changes  in  the 
floor  of  the  fourth  ventricle  cause  real  diabetes,  and  Bernard's  punc- 
ture has  been  a  factor  of  great  importance  in  our  comprehension  of 
diabetes  mellitus. 

Eckhard  found  that  stimulation  of  a  part  of  the  vermis  ("lobus 
hydruricus  et  diabeticus  ")  is  followed  by  polyuria  and  glycosuria. 

Lesions  of  various  parts  of  the  brain  may  cause  glycosuria,  as 
Schiff  saw  after  section  of  the  optic  lobes,  the  pedunculi  cerebri, 
and  the  central  and  posterior  parts  of  the  pedunculi  cerebelli. 

Glycosuria  often  occurs  after  trauma  of  the  brain.  Higgins  and 
Ogden  found  it  in  20  out  of  212  cases.  This  glycosuria  generally 
passes  off"  in  a  few  days  ;  now  and  then  true  diabetes  mellitus  or 
insipidus  remains.  Though  Asher  has  collected  124  cases  of  trau- 
matic diabetes  mellitus,  I  repeat  that  trauma  is  a  rare  cause  of 
diabetes  mellitus  in  adults. 

Section  of  the  spinal  cord  down  to  the  fourth  cervical  vertebra 
is  followed  in  the  dog  by  glycosuria  (Pavy,  Chauveau,  and  Kauf- 
mann). 

Section  of  the  spinal  cord  between  the  fourth  cervical  and  the 


GLYCOSURIAS.  33 

sixth  thoracic  vertebra  is  at  first  followed  by  slight  and  transitory 
hyperglycemia,  but  subsequently  by  hypoglycemia.  Incisions 
below  the  sixth  thoracic  vertebra  cause  no  alteration  in  the  quan- 
tity of  the  sugar  in  the  blood  (Chauveau  and  Kaufmann). 

Claude  Bernard  severed  the  spinal  cord  of  a  rabbit  between  the  last  cervical 
and  the  first  dorsal  vertebra.  The  animal  became  paralyzed  below  the  divi- 
sion, and  respiration  became  slower,  and  the  temperature  sank.  The  quantity 
of  sugar  in  the  blood  also  diminished, — as  Chauveau  and  Kaufmann  found 
also  subsequently, — and  the  amount  of  glycogen  in  the  liver  increased.  This 
last  fact  is  denied  by  Chauveau  and  Kaufmann,  who  aver  that  though  the 
liver,  after  this  operation,  certainly  gives  off  less  glucose  to  the  blood,  it  instead 
discharges  more  glycogen  (?). 

If  the  pneumogastric  of  one  side  is  cut  and  the  central  stump  is 
irritated,  glycosuria  follows,  and  persists  for  a  few  hours.  Some- 
times it  arises  merely  in  consequence  of  the  section  (Bernard, 
Eckhard,  Kiilz).  Arthaud  and  Butte  caused  a  more  continuous 
glycosuria  (amounting  almost  to  2  per  cent.)  by  maintaining  an 
inflammatory  process  in  the  central  stump.  Couvreur,  after  sever- 
ing both  pneumogastric  nerves,  saw  glycosuria  develop  in  the 
rabbit,  and  found,  after  the  same  experiment  in  the  pigeon,  that  the 
amount  of  sugar  in  the  blood  first  rises  above,  but  afterward  falls 
below,  the  normal. 

Filehne  saw  glycosuria  appear  on  irritation  of  the  depressor  branch  of  the 
pneumogastric  nerve,  perhaps  from  the  passage  of  the  stimulus  to  the  latter. 

Claude  Bernard  and  others  have  found  that  irritation  of  the 
peripheral  stump  of  the  divided  pneumogastric  nerve  does  not 
cause  any  change  in  the  amount  of  sugar  in  the  blood  under  the 
same  conditions.  Arthaud  and  Butte  and  Lepine  observed  hyper- 
glycemia, and  Morat  hypoglycemia.  These  differences  in  results 
may  possibly  be  explained  by  differences  in  division  of  the  nerve- 
fibers  in  the  trunks  of  the  pneumogastric. 

Niedieck  caused  inflammation  of  the  sciatic  nerve  in  the  rabbit, 
and  found  glycosuria  develop.  The  neuritis  had  spread  to  the 
spinal  cord,  and  at  times  it  had  passed  over  to  the  sciatic  nerve  of 
the  other  side.  Niedieck  considers  that  changes  in  the  spinal  cord 
cause  the  glycosuria,  either  by  directly  modifying  the  abdominal 
circulation  or  by  transmitting  the  irritation  to  the  floor  of  the  fourth 
ventricle. 


34  DIABETES    MELLITUS   AND    GLYCOSURIA. 

Schiff  also  found  that  irritation  of  the  sciatic  nerve  caused  glyco- 
suria, which  might  last  for  several  days  and  reach  two  per  cent. 
This  was  afterward  observed  also  by  Ryndsjun,  Bohm  and  Hoff- 
mann, and  others.  The  expeiiment  does  not  always  succeed  in 
inducing  glycosuria,  although  Kiilz  obtained  it  in  nine  of  ten 
cases. 

Butte  saw  glycosuria  after  irritation  of  the  first  pair  of  dorsal 
nerves.  Frerichs,  Frazer,  and  others  have  observed  glycosuria  in 
the  course  of  rheumatic  inflammation  of  different  nerves,  and  it  is 
probable  that  irritation  of  any  nerve,  if  sufficiently  intense,  may 
bring  about  such  a  result. 

"""^ K  number  of  observations  illustrate  the  influence  of  the  sympa- 
thetic nervous  system  on  the  sugar  in  the  blood. 

As  early  as  1859  Pavy  found  sugar  in  the  urine  after  section  of 
the  nerves  that  proceed  from  the  superior  cervical  ganglion,  or  after 
extirpation  of  the  ganglion. 

Cyon  and  Aladoff  observed  glycosuria  after  section  of  the  inferior 
cervical  ganglion,  of  the  superior  thoracic  ganglion,  and  of  annulus 
Vieusseni. 

Kiilz  found  section  of  the  cervical  sympathetic  trunk  to  cause 
slight  glycosuria  in  four  of  ten  cases  ;  while  irritation  of  the  cen- 
tral stump  several  hours  later  was  followed  by  glycosuria  in  six  of 
the  ten  cases. 

Irritation  of  the  thoracic  division  of  the  sympathetic  nerve  also 
causes  glycosuria  (Pavy). 

Morat  and  Duponc  observed  an  increased  production  of  sugar  in 
the  liver  as  a  result  of  irritation  of  the  splanchnic  nerve. 

Section  of  the  splanchnic  nerves  often  causes  glycosuria.  Hans 
Voit,  however,  failed  recently  to  obtain  this  result  in  the  majority 
of  cases. 

Pincus,  Budge,  and  Lamanski  saw  dogs,  rabbits,  and  cats  die  with 
profuse  diarrhea  and  a  violent  gastro-enteritis  about  twenty-four 
hours  after  extirpation  of  the  celiac  plexus.  By  means  of  the  same 
operation  Munck  and  Klebs  induced  atrophy  of  the  pancreas  and 
glycosuria  ;  while  Lustig  observed  neither  diarrhea  nor  atrophy 
of  the  pancreas,  but  considerable  glycosuria  (with  polyuria),  ace- 
tonuria,  albuminuria,  and  death  in  coma.  Peiper  had  a  similar  ex- 
perience with  rabbits,  the  glycosuria  reaching  from   2.5   to  4  per 


GLYCOSURIAS.  3  5 

cent.,  but  neither  it  nor  the  acetonuria  nor  the  albuminuria  was 
constant. 

A.  and  E.  Cavazzani  found  a  great  increase  in  the  quantity  of  sugar 
in  the  blood  in  the  hepatic  veins  after  mechanic  and  electric  stimu- 
lation of  the  celiac  plexus. 

A.  Cavazzani  and  G.  Soldani,  who  consider  the  production  of 
sugar  in  the  liver  to  be  a  secretion,  like  all  other  secretions,  found 
that  atropin,  which  paralyzes  the  sympathetic  centers  and  diminishes 
secretion,  also  diminishes  the  amount  of  sugar  in  the  hepatic  veins, 
probably  by  paralyzing  the  celiac  plexus. 

Clinical  experience  affords  numerous  illustrations  of  the  depend- 
ence of  the  assimilation  of  carbohydrates  on  the  nervous  system. 
Sugar  has  been  found  in  the  urine  in  cases  of  general  progressive 
paralysis  (Lallier,  Bequerel,  Bond,  Strauss),  of  tabes  dorsalis  (Smith, 
Oppenheim,  Eulenburg,  and  others),  of  multiple  sclerosis  (Weich- 
selbaum,  Mile.  Blaine  Edwards,  Richardiere),  of  paralysis  agitans 
(Huchard,  Topinard,  Naunyn),  of  chorea  minor  (Demme,  and 
others),  of  epidemic  cerebrospinal  meningitis  (Mannkopf),  and  of 
cerebral  meningitis  (Naunyn),  of  syphilis  (Leudet,  Frerichs,  and 
others),  of  aneurysm  and  of  new  growths  (v.  Recklingshausen, 
Frerichs,  Seegen,  Richardson,  Spitzka,  De  Jonge,  and  others),  of 
cerebral  softening  (Naunyn,  and  many  others)  and  cerebral  hemor- 
rhage (Frerichs,  Olivier,  Schiitz,  Jacques  Meyer,  and  others). 
Michael  also  found  a  cysticercus  embedded  in  granulations  in  the 
floor  of  the  fourth  ventricle  in  a  case  of  diabetes. 

The  numerous  cases  of  disease  of  the  brain,  attended  with  the 
presence  of  pathologic  quantities  of  sugar  in  the  urine,  permit  us 
to  conclude  with  certainty  that  a  causal  connection  exists  between 
lesions  of  different  parts  of  the  brain  and  glycosuria ;  but  the 
statistics  on  the  subject  are  of  little  value,  on  account  of  the  great 
frequency  of  glycosuria  independently  of  brain  disease,  the  small 
number  of  cases,  and  the  want  of  uniformity  in  investigation  and  of 
exact  expression  for  the  normal  power  of  assimilation.  It  must  be 
acknowledged  that  in  a  large  number  of  cases  of  brain  disease  there 
is  only  an  insignificant  decrease,  if  any,  in  the  power  of  assimilating 
carbohydrates.  In  only  four  of  Kahler's  twenty-three  cases  of 
organic  disease  of  the  central  nervous  system  was  there  a  distinct 
diminution  in  that  power.     Van  Oordt  ( 1 898)  found  enfeebled  power 


36  DIABETES    MELLITUS    AND    GLYCOSURIA. 

of  assimilating  carbohydrates  in  25  of  178  cases  of  diseases  of  the 
central  nervous  system.  Several  of  the  cases  were  neuroses  (neu- 
rasthenia, hysteria,  traumatic  neurosis).  Epilepsy  and  diseases  of 
the  spinal  cord  seemed  to  cause  a  diminution  in  the  power  of  assimi- 
lation. Van  Oordt's  twenty-five  cases,  however,  do  not  seem  to  me 
to  make  up  a  greater  percentage  with  decreased  power  of  assimilation 
than  is  found,  on  the  average,  among  brain-workers.  Glycosuria 
seems  to  be  most  frequent  in  cases  of  tumor  of  the  brain,  of 
general  progressive  paralysis,  and  of  cerebral  hemorrhage.  The 
intensity  of  the  glycosuria  is  generally  slight,  and  does  not  amount 
to  a  real  diabetes.  Still,  in  cases  of  general  paralysis,  the  amount 
of  sugar  often  reaches  one  per  cent,  or  more,  and  in  cases  of 
tumor  and  hemorrhage  as  much  as  four  per  cent,  has  been  ob- 
served. If  the  patient  survive,  the  glycosuria  following  apoplexy 
generally  is  transitory ;  sometimes  true  diabetes  may  develop 
(Jacques  Meyer).  (For  a  consideration  of  glycosuria  complicating 
tabes  dorsalis  and  multiple  sclerosis  I  refer  to  chapter  II.) 

Cerebral  softening,  or  encephalomalacia,  is  much  more  commonly 
an  effect  than  a  cause  of  diabetes  (Naunyn). 

Exophthalmic  goiter  is  sometimes  attended  with  glycosuria 
(Chvostek,  Dumontpellier,  Panas,  Pavy,  Blocq,  Kraus,  Ludwig,  and 
others),  and  sometimes  with  true  diabetes  (Bettman,  Laache).  I 
have  at  present  under  observation  a  case  of  diabetes  with  struma, 
tachycardia,  and  nervous  symptoms,  but  without  exophthalmos. 

A  diminished  power  of  assimilation  of  carbohydrates  in  different 
degrees  has  often  been  observed  in  cases  of  akromegaly  also 
(Pierre-Marie,  Cunningham,  Lancereaux,  and  others).  Marinesco 
has  recorded  a  case  of  akromegaly  with  diabetes  mellitus,  epilepsy, 
and  bilateral  hemianopsia. 

Epilepsy  is  at  times,  especially  after  attacks,  attended  Avith  gly- 
cosuria (Goolden,  Griesinger,  Lallier,  Ringer,  Barlow,  and  others). 
"  Mais  elle  (la  glycosurie)  reste  en  somme  une  manifestation  excep- 
tionelle  "  ("  Les  Epilepsies,  "  Ch.  Fere,  Paris,  1890). 

Pathologic  quantities  of  sugar  have  also  been  discovered  in  the 
urine  in  cases  of  meningomyelitis  (Kunkler),  of  myelitis  (Bequerel), 
of  spinal  hemorrhage  (Siebert,  Scharlau,  Vogler),  of  fracture  and 
contusion    of  the    cervical  and    dorsal  vertebrae  (Schiff,  Frerichs, 


GLYCOSURIAS.  37 

Fischer),  and  of  spondylitis  (Baum).  May  found  glycosuria  and 
levulosuria  in  a  case  of  transverse  myelitis. 

Traumatic  neuroses  are  often  accompanied  by  glycosuria  (Brou- 
ardel,  Richardiere,  Strauss,  von  Striimpell,  Ebstein,  Naunyn,  and 
others). 

Simple  neuralgias  also — especially  of  the  fifth  pair — and  sciatica 
are  often  complicated  by  glycosuria.  I  recently  found  one  per 
cent,  of  sugar  in  the  urine  in  a  case  of  violent  sciatica  without  any 
other  symptoms  of  diabetes. 

I  consider  it  one  of  my  most  important  tasks  to  emphasize  the 
glycosuria  so  often  found  in  cases  of  acute  or  chronic  "  functional  " 
nervous  disturbances,  and  for  which  there  is  no  better  name  than 
functional  nervous  glycosuria. 

Such  a  pathologic  excretion  of  sugar  may  be  the  effect  of  an 
entirely  transitory  nervous  disturbance,  and  may  appear  in  other- 
wise healthy  individuals  for  only  a  few  hours  after  some  powerful 
emotion  (as  of  fear  or  anger),  such  as  in  a  case  of  more  permanent 
glycosuria,  or  in  one  of  true  diabetes,  may  for  a  short  while  greatly 
increase  the  quantity  of  sugar  in  the  urine.  Almost  every  physi- 
cian who  has  given  much  attention  to  a  study  of  the  urine  will  have 
encountered  instances  of  such  transitory  glycosuria,  of  which  a 
large  number  are  recorded  in  literature.  Many  facts  tend  to  show 
that  a  similar  condition  occurs  not  rarely  in  animals,  especially 
among  the  higher  classes  of  vertebrates.  Paul  Gib  has  recently 
given  the  account  of  a  bitch  that  always  objected  strongly  to  being 
shut  up,  and  was  greatly  agitated  during  her  seclusion,  and  that 
constantly  after  such  treatment,  but  never  otherwise,  presented 
small  quantities  of  glucose  (up  to  0.55  per  cent.)  in  the  urine. 

Such  an  effect  of  transitory  emotions  makes  it  difficult  in  many 
cases  to  determine  the  nature  of  an  excretion  of  sugar  both  in  man 
and  in  animals.  Glycosuria  following  an  attack  of  gall-stones  (as 
observed  by  Finkler  and  Gans)  may  be  caused  by  the  simple  irrita- 
tion of  peripheral  nerves,  or  by  hyperemia  of  the  liver  ;  but  it  may 
also  be  the  effect  of  the  mere  mental  anguish  of  the  patient  during 
the  painful,  and  possibly  dangerous,  passage  of  a  gall-stone.  Stu- 
dents of  experimental  pathology  should  bear  in  mind  this  possible 
cause   of  a  transitory  glycosuria  of  doubtful   origin,  and  there  is 


38  DIABETES    MELLITUS    AND    GLYCOSURIA. 

abundant  evidence  that  it  often  occurs  in  laboratories,  where  the 
infliction  of  pain  on  animals  is  not  always  avoidable.  Minkowski 
discovered  glycosuria  in  1 5  of  32  animals  subjected  to  operative 
experiments,  in  which  this  phenomenon  probably  must  be  attrib- 
uted to  mental  influences.  Examination  of  the  figures  given  by 
Pavy,  McDonnel,  Seegen,  Abeles,  and  others,  for  the  quantity  of 
sugar  in  the  blood  of  the  hepatic  veins  during  experiments  on  ani- 
mals leads  to  the  conclusion  that  the  experiment  increases  the  pro- 
duction of  sugar  in  the  hver  through  the  mere  suffering  it  causes. 
It  is  not  at  all  improbable  that  the  glycosuria  that  follows  extirpa- 
tion of  the  salivary  glands,  so  much  expatiated  upon  by  Reale  and 
Rienzi,  or  that  observed  by  Schiff  after  the  ligation  of  the  femoral 
artery,  or  by  Minkowski  after  resection  of  the  duodenum,  as  well 
as  other  slight  and  inconstant  varieties  of  excretion  of  sugar  in  the 
urine,  are  to  be  referred  to  this  category.* 

Bohm's  and  Hoffmann's  "  Fesselungsglycosurie  "  in  the  cat,  sub- 
sequent to  its  being  tied  experimentally,  is  well  known,  and  can  be 
explained  most  easily  by  the  mental  state  and  emotion  produced 
by  such  treatment,  though  asphyxia  may  also  be  operative  in  this 
instance.  The  same  may  be  said  of  Velisch's  observation  of  gly- 
cosuria in  the  frog  after  tying  it  on  its  back,  or  after  keeping  it  on 
its  head  in  a  narrow  cylinder. 

In  some  cases  nervous  glycosuria  may  last  for  some  length  of 
time,  but  finally  disappears. 

L,  a  medical  student,  works^hard  at  his  books,  and  is  alarmed  now  and 
then  to  find  distinct  reactions  with  the  ordinary  tests  for  sugar  in  his  urine, 
which  after  rest  and  a  trip  to  a  warmer  climate  becomes  normal. 

X,  a  youth  of  nineteen,  was  for  several  years  addicted  to  masturbation,  and 
every  evening  after  dinner  presented  about  o.i  per  cent,  of  sugar,  which  dis- 
appeared some  time  after  he  reformed  his  ways. 

Mrs.  T,  now  seventy-six  years  old,  during  middle  age  and  after  a  period  of 
great  anxiety,  excreted  daily  more  or  less  than  a  gram  of  glucose  with  the 
urine.  This  caused  her  family  some  uneasiness,  especially  as  a  daughter 
had  died  of  diabetes ;  but  at  present  the  old  lady's  urine  exhibits  no  trace  of 
reaction  two  hours  after  an  abundant  mixed  meal. 


*  Falkenberg  and  Kulz  observed,  after  extiipation  of  the  thyroid  gland,  glycosuria 
that  was  not  constant,  though  it  sometimes  lasted  for  weeks.  Naunyn,  in  his  recently 
published  monograph,  probably  coiTectly  explains  this  glycosuria  by  the  starvation  con- 
sequent upon  the  operation. 


GLYCOSURIAS.  39 

Count  X  Y  Z,  in  a  scientific  controversy,  both  made  and  committed  to  paper 
a  number  of  most  absurd  statements,  for  which  he  was  subjected  to  severe 
but  well-deserved  criticism,  by  which  he  was  greatly  affected.  During  this 
time  he  availed  himself  of  the  opportunity  to  make  some  interesting  investi- 
gations concerning  the  influence  of  emotion  on  metabolism,  and  on  various 
occasions  he  found  as  much  as  0.3  per  cent,  of  glucose  in  his  urine.  After  he 
had  returned  to  the  intellectual  passivity  for  which  nature  evidently  intended 
him,  and  time  had  consoled  him  for  his  disappointments,  his  urine  returned  to 
its  natural  condition. 

If,  on  the  other  hand,  the  nervous  causes  of  glycosuria  are  pro- 
longed or  become  permanent,  so  will  also  the  excretion  of  sugar 
with  the  urine,  and  this  may  continue  for  many  years,  and  often  for 
the  rest  of  life.  These  habitual  glycosurias  have  exactly  the  same 
etiology  as  true  diabetes  ;  and  there  will  be  found  to  exist  heredi- 
tary influences  of  a  diabetic,  a  nervous,  or  a  gouty  nature,  and  the 
usual  accidental  influences  :  viz.,  painful  emotions,  intellectual 
overwork,  sexual  excesses,  etc. 

Habitual  glycosuria  is  found  especially  in  persons  suffering  from 
those  common  functional  disorders  grouped  under  the  name  of 
neurasthenia,  which  disorders,  when  once  they  have  appeared, 
seldom  entirely  leave  the  patient. 

Among  neurasthenic  patients,  again,  we  may  expect  to  find 
pathologic  quantities  of  sugar  in  the  urine,  especially  in  cases  com- 
plicated by  gout  or  obesity  ;  and  it  is  a  matter  of  choice  whether 
we  ascribe  the  glycosuria  to  the  neurasthenia  or  consider  it  a  col- 
lateral symptom  of  the  obesity  or  gout,  which  latter  dystrophy,  by 
the  way,  is  accompanied  with  marvelous  constant  nervous  symp- 
toms. Among  obese  persons  we  also  not  rarely  find  glycosuria, 
especially  in  those  that  exhibit  neurasthenic  stigmata.  There  is 
among  the  upper  social  classes  a  not  rare  type  of  middle-aged  man, 
with  a  bodily  weight  as  often  above  as  below  200  pounds,  with 
ruddy  cheeks  and  a  general  appearance  of  health,  but  with  high- 
strung  nerves,  great  sensitiveness,  and  often  with  some  slight  gouty 
trouble.*     If  we  adopt  the  rule  of  testing  our  patients'  urine  an 

*  As  has  already  been  mentioned,  diabetes  insipidus,  like  obesity  and  gout,  may  be 
converted  into  diabetes  raellitus  or  it  may  be  attended  with  the  excretion  of  a  small 
amount  of  sugar  in  the  urine  (Senator,  Legroux).  Such  cases,  however,  seem  to  be  quite 
rare,  even  comparatively.  In  the  rare  cases  of  recovery  from  diabetes  mellitus  a  distinct 
diabetes  insipidus  sometimes  remains. 


40  DIABETES    MELLITUS    AND    GLYCOSURIA. 

hour  after  dinner,  we  shall  find  in  a  large  proportion  of  the  repre- 
sentatives of  the  type  described  at  least  distinctly  pathologic  traces 
of  sugar — simple  glycosuria.  In  other  cases  we  shall  find  a  true, 
though  mild,  diabetes. 

Wherever  we  turn  we  often  see  in  practice  illustrations  of  the 
close  relationship  between  all   stages  of  the  glycosuric  dystrophy. 

In  a  family  of  eight  children  one  sister  died  at  twenty-nine  in  diabetic  coma  ; 
another,  who  subsequently  died  of  carcinoma,  developed  the  mild  type  of  dia- 
betes when  about  fifty  years  of  age ;  in  a  third,  somewhat  corpulent,  but  other- 
wise healthy,  sister,  I  have,  in  the  course  of  many  years,  found  several  times 
after  meals  from  o.  i  to  0.2  per  cent,  of  sugar  in  the  urine.  With  the  exception 
of  the  sister  that  died  in  coma,  none  of  the  family  presents  any  nervous  dis- 
order, but  on  the  father's  side  there  are  neuropathic  individuals  of  closest 
relationship. 

In  different  branches  of  another  well-known  and  widely  spread  family  I 
have  seen  simple  glycosuria,  mild  and  severe  diabetes,  gout,  and  obesity,  with 
or  without  traces  of  sugar.  The  psychopathic  element  in  this  in  part  highly 
intellectual  family  has  manifested  itself  in  fully  developed  psychoneuroses,  in 
dipsomania,  in  perverted  sexual  desires,  and  in  eccentricity. 

The  son  of  a  man  who  met  his  death  by  diabetic  coma  discovered  in  late 
middle  age  that  he  was  excreting  sugar,  the  condition  being  found  to  be  one  of 
slight  simple  glycosuria.  The  daughter  of  a  woman  who  had  presented  slight 
glycosuria  died  in  early  life  of  severe  diabetes,  and  so  on. 

The  daily  excretion  of  sugar  in  the  urine  in  cases  of  simple  glyco- 
suria is  always  insignificant,  and  the  amount  is  frequently  so  small 
that  it  can  not  with  certainty  be  demonstrated  in  larger  quantities 
of  urine,  even  after  abundant  ingestion  of  carbohydrates.  If  in  a 
sample  of  the  urine  collected  during  twenty-four  hours  a  percentage 
of,  for  instance,  0.5  be  found,  the  case  can  no  longer  be  classed  as 
one  of  simple  glycosuria,  unless  special  causes — such  as  excessive 
indulgence  in  alcohol,  an  acute  infection,  powerful  emotion,  and  the 
like — have  contributed  to  the  condition.  The  quantity  in  small 
samples  voided  a  certain  time  (from  one  to  two  hours)  after  meals 
varies  from  hundredths  to  tenths  of  a  per  cent.,  and  may  for  a  little 
while,  under  the  influence  of  agencies  that  increase  the  secretion, 
reach  a  somewhat  higher  figure.  A  percentage  of  1.5,  even  in 
small  quantities  of  urine,  is  rare  in  cases  of  simple  glycosuria  ;  more 
than  2  per  cent,  scarcely  occurs  at  all  in  an  anomaly  of  this  kind. 

Simple  glycosuria  causes  of  itself — /.  c,  by  hyperglycemia  and  by 
loss  of  sugar — no  symptoms  at  all  or  only  ill-defined  and  transitory 


GLYCOSURIAS.  4 1 

symptoms.  We  find  in  these  cases,  beyond  the  small  quantities  of 
glucose  in  the  urine,  usually  no  pathologic  manifestations  except 
the  various  neurasthenic  stigmata  and  symptoms  in  lesser  or  greater 
number,  and  these  can  not  possibly  be  ascribed  to  the  insignificant 
deficiency  in  the  power  of  assimilating  carbohydrates  or  to  the  small 
addition  to  the  normal  quantity  of  sugar  in  the  blood,  which  addition 
probably  amounts  to  determinable  quantities  only  for  a  compara- 
tively short  part  of  the  twenty -four  hours.  To  avoid  unnecessary 
repetitions,  I  refer  to  chapter  iv  for  a  consideration  of  those  neuras- 
thenic symptoms,  of  which  the  most  frequent  and  the  most  distress- 
ing are  an  excessive  emotional  irritability,  insomnia,  and  enfeebled 
virility.  I  wish  here  only  to  remark  that  the  glycosuria  stands  in 
no  fixed  relation  to  the  intensity  of  the  neurasthenic  neurosis.  We 
may  find  glycosuria  present  in  casQS  of  but  slightly  developed  neu- 
rasthenia, and  we  may  look  in  vain  for  it  in  cases  in  which  many 
stigmata  and  symptoms  combine  to  bring  out  in  strong  relief  the 
neurasthenic  picture  which  is  scarcely  ever  complete  in  the  indi- 
vidual case. 

The  symptoms  that  may  be  caused  by  hyperglycemia  and  glycosuria  in 
these  cases  are  so  vague  that  even  a  considerable  experience  and  much  atten- 
tion have  not  enabled  me  to  arrive  at  definite  conclusions  with  regard  to  some 
points.  PoUakiuria,  or  increased  frequency  of  micturition,  even  though  the 
quantity  of  urine  expelled  at  each  voidance  be  small,  is  a  usual,  though  not 
constant,  symptom  in  cases  of  simple  glycosuria.  It  is,  however,  common  also 
in  "  nervous  "  patients  without  glycosuria,  and  it  is  often  noticeable  whenever 
the  urine  contains  any  great  amount  of  crystals  of  calcium  oxalate,  which  is 
often  the  case  in  the  presence  of  simple  glycosuria. 

I  have  found  furunculosis  in  quite  a  number  of  cases,  with  such  an  insig- 
nificant excretion  of  sugar  that  I  could  not  possibly  class  them  among  diabetics. 
Furunculosis  is  also  one  of  the  earliest  symptoms  of  mild  diabetes.  With 
regard  to  furunculosis,  also,  we  must  remember  the  oxaluria  so  common  in 
neurasthenic  patients,  and  especially  in  those  that  show  glycosuria.  In  the 
"idiopathic  oxaluria"  of  Begbie,  Cantani,  and  others,  the  clinical  picture  is 
made  up  of  slight  nervous  and  dystrophic  symptoms,  and  among  the  latter  the 
authors  also  name  furunculosis.  It  is  not  improbable  that  other  causes  than 
hyperglycemia  are  here  active,  especially  in  view  of  the  fact  that  furunculosis  is 
much  more  frequent  in  mild  than  in  severe  cases  of  diabetes. 

Other  cutaneous  eruptions,  especially  eczema,  are  sometimes  found  in  cases 
of  simple  glycosuria,  which,  like  diabetes,  frequently  arise  in  persons  with 
vasomotor  irregularities  of  different  kinds.  It  is  difficult  to  assert  any  direct 
connection  between  these  cutaneous  troubles  and  glycosuria ;  they  are  both 
often  found  in  cases  of  gout — a  frequent  disease  in  glycosuric  individuals. 
4 


42  DIABETES    MELLITUS   AND    GLYCOSURIA. 

Patients  aware  of  the  presence  of  slight  quantities  of  sugar  in  their  urine 
sometimes  mention  dryness  of  the  mouth  or  increased  thirst,  but  the  quantity 
of  urine  rarely  exceeds  20  cu.  cm.  to  the  kilogram  of  body  weight. 

The  teeth,  which  in  true  diabetes  are  pretty  certain  to  be  carious  and  defec- 
tive after  some  years,  are  often  in  most  excellent  condition  after  decades  of 
simple  glycosuria. 

When  the  physician  wishes  to  determine  by  careful  investigation 
as  far  as  possible  the  nature  of  a  slight  glycosuria,  and  to  give  it  a 
name,  he  must  fully  understand  that  his  task  is  entirely  a  practical 
one,  and  that  he  must  give  up  all  attempts  to  draw  a  distinct,  sci- 
entific limitation  between  simple  glycosuria  and  diabetes.  While 
bearing  in  mind  that  simple  glycosuria  and  glycosuria  in  mild  and 
severe  cases  of  diabetes  represent  only  a  dystrophic  symptom  of 
various  pathologic  states  and  processes,  we  must  remember  that 
exactly  the  same  gradual  differences  are  to  be  observed  in  the  excre- 
tion of  sugar  as  in  other  dystrophic  manifestations.  What  inteUi- 
gent  physician  would  undertake  to  determine  where  gout  begins  ? 
In  obesity,  which  reveals  itself  to  our  senses  much  more  readily 
than  gout  or  diabetes,  even  the  layman  understands  that  the  interval 
between  the  normal  man  and  the  representative  of  the  highest 
degree  of  obesity  may  be  filled  by  a  thousand  individuals  in  such  a 
manner  that  only  a  minute  difference  exists  between  each  man  and 
his  neighbor  to  the  right  and  to  the  left  in  the  long  line.  We  meet 
with  exactly  analogous  conditions  in  glycosuric  patients.  It  is  im- 
possible to  decide  precisely  when  the  faint  trace  of  sugar  that,  we 
must  allow,  may  appear  in  normal  urine  ceases  to  be  normal  and 
passes  over  into  simple  pathologic  glycosuria.  It  is  equally  im- 
possible to  find  the  boundary-line  between  the  latter  and  mild  dia- 
betes, and  in  the  chapter  on  metabolism  we  shall  find  that  mild  and 
severe  "forms"  of  diabetes  are  also  connected  by  intermediate 
stages.  The  individual  may  sometimes,  by  slow  degrees,  and  dur- 
ing a  series  of  years,  pass  through  all  stages,  from  the  normal  state 
to  that  in  which  he  is  overtaken  by  death  from  diabetic  coma. 
This,  however,  is  not  the  usual  course,  and  many  patients  remain 
in  the  vicinity  of  that  place  in  the  chain  that  they  occupied  a  short 
time  after  the  beginning  of  their  dystrophy.  Simple  glycosuria, 
as  already  mentioned,  often  shows  a  decided  tendency  to  remain 
unaltered  for  decades,  in  spite  of  all  sorts  of  pernicious  influences. 


GLYCOSURIAS.  43 

Mild  diabetes  certainly  not  infrequently  develops  gradually  from 
simple  glycosuria,  but  it  also  often  appears  at  once  or  after  a  short 
time  as  mild  diabetes,  and  usually  remains  mild  diabetes.  If  we 
can  not  deny  that  the  severe  type  sometimes  has  gradually  been 
evolved  from  the  mild,  it  much  more  frequently  shows  itself  in  its 
severe  character  a  short  time  after  a  normal  state. 

In  examining  and  forming  an  opinion  on  a  case  with  a  small 
amount  of  sugar  in  the  urine,  the  physician  must  further  always 
bear  in  mind  that,  as  simple  glycosuria  may,  under  some  temporary 
influence,  momentarily  resemble  mild  diabetes,  so  also  may  mild 
diabetes  at  times  appear  exactly  like  simple  glycosuria,  and  that, 
consequently,  repeated  examinations  are  always  necessary.  Re- 
cently I  examined  two  patients  on  the  same  day — Mrs.  M.  and 
Mr.  R.,  both  about  forty  years  of  age.  An  hour  after  a  similar 
dinner  of  mixed  food  the  urine  of  each  contained  fully  o.  1 5  per 
cent,  of  glucose,  although  in  the  urine  collected  for  the  twenty -four 
hours  there  was  a  scarcely  perceptible  trace.  The  patients  con- 
sumed 200  grams  of  cane-sugar  each  ;  the  urine  in  neither  case 
afterward  yielded  a  distinct  reaction  with  Nylander's  solution,  but 
in  both  cases  reduced  abundantly  after  boiling  with  a  few  drops  of 
sulphuric  acid.*  In  short,  the  two  cases  seemed  for  the  moment 
to  be  as  similar  as  they  could  be.  They  are,  however,  essentially 
different  in  nature.  Mr.  R.  for  fully  ten  years  has  exhibited  a  sim- 
ple, neurasthenic  glycosuria,  which  during  all  this  time,  and  with 
ordinary  food,  has  appeared  as  it  does  now,  without  ever  reaching 
considerable  quantities  of  sugar  or  giving  rise  to  diabetic  symp- 
toms ;  it  will  in  all  probability  remain  stationary  in  the  future. 
Mrs.  M.  suffers  from  a  true,  though  mild,  diabetes  of  several  years' 
standing.  A  few  weeks  ago  her  urine  contained  over  two  per  cent, 
of  sugar,  and  there  was  some  polyuria  ;  she  has  reached  her  present 
power  of  assimilation  only  after  several  weeks  of  strict  diet.  If  she 
should  for  any  length  of  time  indulge  in  a  free  diet,  which  now  was 
occasionally  allowed  for  a  couple  of  days  for  the  sake  of  the  experi- 
ment, her  old  symptoms  would  be  certain  to  reappear. 

In  other  rare  cases  the  same  individual  may,  without  any  dififer- 


*  In  other  words,  neither  urine  contained  glucose,  but  both  urines  contained  some 
cane-sugar,  which,  after  being  inverted  by  boiling  with  acid,  reduced  (see  below). 


44  DIABETES    MELLITUS    AND    GLYCOSURIA. 

ence  in  diet,  and  without  any  assignable  cause,  present  a  periodic 
alternation  of  simple  glycosuria  and  true,  though  mild,  diabetes. 
This  is  the  condition  that  now  and  again  is  mentioned  in  medical 
literature  as  periodic  diabetes.  In  the  cases  of  this  kind  that  have 
come  under  my  observation  a  distinctly  pathologic,  though  com- 
paratively insignificant,  trace  of  glucose  is  found  even  during  the 
"  free"  intervals.  Such  a  case  is  that  of  the  Countess  H.,  who  has 
been  under  my  observation  for  several  years.  The  lady,  who  is 
somewhat  over  forty  and  very  corpulent,  shortly  after  her  husband's 
death  began  to  suffer  from  constant  thirst.  The  polydipsia  excited 
the  attention  of  the  servants,  and  the  family  physician  found  con- 
siderable quantities  of  sugar  in  the  urine.  Since  then,  this  most 
conscientious  patient  has  for  several  years  constantly  adhered  to 
the  same  diet,  with  a  considerable  reduction  of  carbohydrates  (lOO 
grams  of  bread  a  day  and  some  vegetables  and  animal  food).  Once 
or  twice  a  year,  at  intervals  of  varying  length,  diabetic  symptoms 
appear  for  some  weeks,  with  the  excretion  of  considerable  amounts 
of  sugar  (from  20  to  25  grams  daily),  but  these  soon  disappear, 
even  if  no  change  is  made  in  the  dietetic  regimen.  In  the  intervals 
the  urine  for  twenty-four  hours  shows,  with  Nylander's  and 
Fehling's  solutions,  just  appreciable  traces  of  sugar.  At  present 
the  patient  has  just  passed  through  a  new  diabetic  period,  which, 
unlike  the  previous  attacks,  continued  for  five  months,  until,  when 
she  appeared  again  in  Carlsbad,  I  reduced  for  some  time  the  carbo- 
hydrates to  a  minimum.  The  patient  is  now  able  to  take  eighty 
grams  of  bread  daily,  together  with  some  vegetables,  without  show- 
ing more  than  traces  of  glucose  in  the  urine,  which  will  be  ex- 
amined more  frequently  in  order  to  effect  without  delay  any  reduc- 
tion in  carbohydrates  that  may  possibly  be  necessary.  I  consider 
it  probable  that  the  case  will  develop  into  a  common,  persistent, 
mild  diabetes. 

Very  likely  similar  cases,  complicated  by  gout,  have  been  designated  "  dia- 
betes alternans''  ever  since  the  time  of  Peter  Franks.  By  this  appellation  is 
generally  meant  a  state  in  which  alternately  sugar  and  uric  acid  in  abundant 
quantities  appear  in  the  urine.  Gouty  patients  often  present  either  simple  glyco- 
suria or  an  especially  mild  diabetes.  With  the  periodic  increase  in  the  power  of 
assimilation,  which  may  occur  in  such  cases,  the  amount  of  sugar  in  the  urine 
falls  to  a  minimum.  That  a  real  alternation  occurs,  so  that  the  quantity  of  uric 
acid  increases  as  the  quantity  of  sugar  in  the  urine  diminishes,  and  vice  versa. 


GLYCOSURIAS. 


45 


is  at  any  rate  not  proved,  and  among  the  large  number  of  gouty  and  glycosuric 
patients  that  I  have  treated  I  have  not  been  able  to  find  a  single  case  in  which, 
as  a  result  of  the  considerable  analytic  work  necessary,  the  slightest  evidence 
of  such  an  alternation  was  detected.  It  is  difficult  to  understand  how  the 
presence  of  uric  acid  in  the  urine  should  bear  any  fixed  relation  to  the  gly- 
cosuria. 

A  connection  between  glycosuria  and  the  presence  of  oxalic  acid 
in  the  urine — the  molecular  construction  of  the  latter  giving  it  a 
position  between  glucose  on  the  one  hand,  and  water  and  carbonic 
acid  on  the  other — has  a  good  theoretic  basis,  and  I  have  seen 
cases  of  simple  glycosuria  that,  when  free  from  glucose,  have  pre- 
sented marked  oxaluria. 

Though  no  exact  dividing-line  can  be  drawn  between  adjacent 
cases  of  the  one  and  the  other,  a  comparison  between  the  typical 
forms  of  simple  glycosuria  and  of  true  though  mild  diabetes  will 
show  several  practically  important  differences  : 


Glycosuria. 
Smaller  quantity  of  glucose  which,  even 
after  abundant  and  protracted  inges- 
tion of  carbohydrates,  seldom  rises  to 
any  considerable  fraction  of  one  per 
cent,  in  the  urine  for  twenty-four 
hours,  and  altogether  only  amounts  to 
a  very  small  number  of  grams. 

The  excretion  of  glucose  is  in  less  definite 
relation  to  the  amount  of  carbohydrate 
ingested.  The  patient  may  show 
some  glycosuria  after  a  hearty  dinner, 
but  may  be  capable  of  ingesting  large 
quantities  of  cane-sugar  or  rice  with- 
out glycosuria  making  its  appearance, 
Emotions,  alcohol,  etc.,  have  a  very 
conspicuous  influence  in  inducing  gly- 
cosuria. 

The  amount  of  glucose,  therefore,  under 
the  same  dietetic  conditions,  though 
always  small,  undergoes  comparatively 
wide  variations. 

Simple  glycosuria  gives  rise  to  no  distinct 
diabetic  symptoms,  except  the  patho- 
logic amount  of  sugar  in  the  urine. 


Mild  Diabetes. 

Larger  quantity  of  glucose  which,  after 
abundant  and  protracted  ingestion  of 
carbohydrates,  always  reaches  large 
fractions  of  one  per  cent.,  and  usually 
more  than  one  per  cent,  in  the  urine 
for  twenty-four  hours,  the  whole  ex- 
cretion, under  such  circumstances,  al- 
ways amounting  to  several  grams. 

The  excretion  of  glucose  is  in  a  more  defi- 
nite relation  to  the  amount  of  carbo- 
hydrate ingested,  though  it  may  be 
increased  by  emotional  and  other  in- 
fluences. 


The  amount  of  glucose  under  the  same 
dietetic  conditions  usually  varies  less 
than  in  simple  glycosuria. 

True  diabetes,  though  mild,  generally  upon 
a  free,  mixed  diet  gives  rise  to  other 
symptoms  than  glycosuria,  especially 
to  polydipsia  and  polyuria. 


46 


DIABETES    MELLITUS    AND    GLYCOSURIA. 


Glycosuria. — {^Continued.') 

Simple  glycosuria  has  a  more  stationary 
tendency,  and  is  often  attended  for 
decades  with  the  same  power  of  as- 
similating carbohydrates. 


After  the  ingestion  of  a  large  dose  of  some 
other  saccharid  than  glucose,  a  certain 
amount  of  that  saccharid  appears  in 
the  urine,  accompanied  by  no  glucose 
or  by  a  relatively  small  amount  of  it. 


Mild  Diabetes. — [Contimied.) 

True  diabetes,  even  in  its  mild  stage,  has 
a  more  progressive  tendency.  The 
power  of  assimilating  carbohydrates 
often  gradually  diminishes,  and  the 
mild  stage  not  very  rarely  passes  over 
into  the  severe  stage. 

After  a  large  dose  of  some  other  saccharid 
than  glucose,  a  certain  amount  of  glu- 
cose appears  in  the  urine  accompa- 
nied by  no  other  saccharid  or  by  a 
comparatively  small  amount  of  the 
ingested  saccharid. 


The  late  excellent  Norwegian  physiologist  and  speciaUst  in 
diabetes,  Worm-Mviller,  considered  that  he  had  discovered  a  dis- 
tinct difference  between  glycosuria  and  diabetes  in  their  different 
behavior  after  the  ingestion  of  large  amounts  of  other  saccharids 
than  glucose.  In  simple  glycosuria,  according  to  this  observer, 
some  part  of  a  large  amount  of  another  saccharid  ingested  would 
pass  unaltered  in  the  urine,  while  in  diabetes  every  trace  of  sac- 
charid found  in  this  secretion  appears  in  the  form  of  glucose. 
Thus,  in  a  case  presenting  pathologic  excretion  of  glucose  after  the 
ingestion  of  from  200  to  300  grams  of  cane-sugar,  one  of  three 
different  conditions  of  the  urine  would  arise  : 


If  cane-sugar  only  is  found  in  the  urine,  the  urine  reduc- 
ing Fehling's  or  Nylander's  solution  not  previously, 
but  only  subsequently,  to  boiling  with  dilute  sulphuric 
acid, 

If  both  cane-sugar  and  glucose  are  found  in  the  urine, 
greater  reduction  taking  place  after  than  before  boiling 
with  dilute  sulphuric  acid,* 

If  the  urine  contains  only  glucose,  and  the  reduction  is 
as  marked  before  as  after  boiling  with  dilute  sulphuric 
acid. 


diagnosis     of    glycosuria 
must  be  made. 


a    diagnosis    of    glycosuria 
must  be  made. 

a  diagnosis  of  diabetes  must 
be  made. 


*  I  would  remind  the  reader  that  in  this  experiment  titration  and  not  polarization 
must  be  used  before  and  after  boiling  with  dilute  sulphuric  acid.  Before  the  boiling, 
the  glucose  alone  reduces  ;  the  cane-sugar  does  not.  Both  saccharids  turn  the  polarized 
light  to  the  right.  By  boiling,  the  cane-sugar  is  changed  into  "  invert  sugar,"  a  mixture 
of  levulose  and  glucose,  of  which  the  former  turns  the  polarized  ray  of  light  to  the  left, 
while  the  latter  turns  it  to  the  right,  but  both  have  about  the  same  capacity  for  reduction 
(see  below). 


GLYCOSURIAS.  47 

This  mode  of  distinguishing  between  diabetes  and  simple  glyco- 
suria has,  however,  only  relative  value,  and  we  find  also  in  this 
respect  only  a  gradual  difference.  In  diabetes  (except  in  some 
cases  after  long  periods  of  abstinence  from  carbohydrates)  glucose 
is  far  more  easily  made  to  appear  in  the  urine  after  ingestion  of 
cane-sugar  than  in  simple  glycosuria,  and  after  certain  amounts  in 
the  former  only  glucose  may  be  found  in  the  urine  ;  but  after  large 
amounts  of  cane-sugar  even  the  diabetic  patient  of  the  most  aggra- 
vated type  may  pass,  in  addition  to  large  quantities  of  glucose, 
small  quantities  of  unaltered  cane-sugar.  Minkowski  found  this 
to  be  the  case  even  in  diabetic  dogs  after  the  extirpation  of  the 
pancreas,  though  the  dog — judging  from  many  experiments  re- 
corded in  literature — is  more  prone  than  man  to  develop  glycosuria 
after  ingestion  of  cane-sugar.  In  several  cases  of  slight  simple 
glycosuria  I  have  found  the  proportion  between  the  amounts  of 
cane-sugar  and  glucose  excreted  after  the  ingestion  of  large 
amounts  of  the  former  to  vary  greatly  from  one  day  to  another  in 
the  same  individual.  In  one  case  of  simple  glycosuria  of  long  and 
stationary  standing  in  a  gouty  and  neurasthenic  individual,  the 
patient,  to  overcome  his  dread  of  diabetes,  used  once  every  year 
to  take  300  grams  of  cane-sugar.  The  urine,  which  some  time 
after  every  rich  dinner  contained,  for  a  while,  a  small  amount  of 
glucose,  after  this  enormous  dose  of  cane-sugar  yielded  no  distinct 
reaction  with  Nylander's  solution,  although  it  contained  a  few 
grams  of  unaltered  cane-sugar.  One  day,  however,  just  after 
taking  the  300  grams  of  cane-sugar,  the  patient  got  into  a  violent 
passion,  and  an  hour  afterward  a  small  amount  of  urine  contained 
1.3  per  cent,  of  glucose,  but  only  a  small,  doubtful  amount  of 
cane-sugar.  The  test  being  repeated  some  few  days  later,  yielded 
the  former  usual  result ;  the  urine  contained  no  definite  amount  of 
glucose,  but  a  few  grams  of  cane-sugar. 

Simple  glycosuria  does  not  perceptibly  alter  the  "  patient's  "  state 
of  nutrition,  and  generally  shows  a  strong  tendency  to  remain  sta- 
tionary, even  under  the  influence  of  deleterious  circumstances.  The 
later  in  life  it  appears,  and  the  longer  it  has  remained  unaltered,  the 
smaller  is  the  danger  of  its  development  into  true  diabetes.  When- 
ever gout  exists  as  a  complication,  the  probability  of  the  glycosuria 


48  DIABETES    MELLITUS    AND    GLYCOSURIA. 

remaining  unaltered  is  exceedingly  great,  and  I  consider  such  ex- 
cretions of  sugar  in  the  urine  in  elderly,  gouty  persons  to  be  of 
small  clinical  importance  ;  but  even  an  inconsiderable  glycosuria, 
after  having  shown  itself  for  a  greater  length  of  time,  is  most  likely 
to  continue  through  the  patient's  whole  life,  and  a  development  into 
true  diabetes  is  not  with  certainty  excluded. 

Hepatogenous  Glycosuria. — The  liver  is  the  organ  in  which  gly- 
cogen is  stored  as  a  reserve  force,  and  the  organ  in  which  this 
glycogen  is  again  converted  into  glucose  and  yielded  up  to  the 
circulation  for  the  purpose  of  generating  energy  by  oxidation.  It 
is  evident,  therefore,  that  certain  disturbances  in  the  activity  of  the 
liver  may  cause  disturbances  in  the  metabolism  of  the  sugar  of  the 
blood,  and  occasion  hyperglycemia  and  glycosuria.  Though  it 
involves  some  repetition,  I  consider  it  best,  for  the  purpose  of  gain- 
ing a  clear  view  of  the  subject,  to  make  a  summary  of  the  different 
ways  in  which  this  may  occur. 

The  supply  of  glucose  to  the  liver  through  the  portal  vein  may 
be  so  large  and  so  sudden  that  even  a  normal  capacity  of  the  liver 
to  convert  the  surplus  into  glycogen  is  overtaxed,  and  the  glucose 
over  and  above  that  which  can  be  stored  in  the  muscles  and  else- 
where, or  be  consumed  in  the  tissues,  enters  the  circulation.  This 
is  evidently  the  case  in  what  we  call  alimentary  glycosuria  after 
very  large  amounts  of  glucose  have  been  taken.  Another  instance 
of  a  similar  form  of  glycosuria — which  with  Claude  Bernard,  who 
first  demonstrated  it,  we  may  call  alimentary,  as  its  origin  is  essen- 
tially the  same — is  that  produced  by  the  injection  into  the  mesen- 
teric veins  or  into  the  portal  vein  of  glucose  or  glycogen  (which  is 
transformed  into  glucose  in  the  blood). 

When  hyperemia  of  the  liver  occurs,  hyperglycemia  may  result 
from  an  increased  production  of  sugar,  either  in  consequence  of  the 
diastatic  ferment  of  the  blood  attacking  the  glycogen  more  vigor- 
ously or  of  the  liver-cells  becoming  more  pronounced  in  their 
specific  activity,  including  the  secretion  of  sugar.  It  is  certain  that 
Bernard's  "piqure,"  many  kinds  of  poison,  and  most  of  those  other 
conditions  that  induce  glycosuria  have  been  shown  to  be  the  cause 
also  of  hyperemia  of  the  liver  ;  and  that  which  directly  causes  hyper- 
emia of  the  liver,  often  causes  also  glycosuria.     Arthaud  and  Butte 


GLYCOSURIAS.  49 

have  recently  shown  that  after  Hgation  of  the  splenic  artery  and  the 
right  gastro-epiploic  artery,  which  considerably  increases  the  supply 
of  arterial  blood  of  the  liver,  glycosuria  arises.  The  finding  by 
Exner  (1898)  of  glycosuria  in  each  of  forty  cases  of  gall-stones 
leads  me  to  believe  that  the  glycosuria  also  in  these  cases  is  due 
to  the  congestion  of  the  liver.  Trauma  of  the  liver  sometimes 
causes  glycosuria — if  through  congestion  or  through  nervous  influ- 
ences is  uncertain.  Hyperglycemia  and  glycosuria  also  follow  if 
arterial  blood  is  injected  into  the  hepatic  artery  (Pavy)  or  if  the  vaso- 
constrictor nerves  of  the  liver  are  divided  (Chauveau  and  Kauf- 
mann).  On  the  other  hand,  anemia  of  the  liver  seems  to  induce 
hypoglycemia.  After  ligation  of  the  hepatic  artery  Arthaud  and 
Butte  found  at  first  hyperglycemia,  probably  brought  on  by  the 
struggles  of  the  animal  during  the  experiment  or  by  the  loss  of  100 
grams  of  blood  taken  before  the  application  of  the  ligature  for  the 
sake  of  determining  the  quantity  of  sugar  (see  below) ;  but  after 
this  transitory  hyperglycemia,  the  ligation  was  followed  by  distinct 
hypoglycemia.  Tangl  and  Harley  also  found  hypoglycemia  after 
ligation  of  the  hepatic  artery. 

Furthermore,  glycosuria  may  arise  from  such  disorders  of  circu- 
lation as  prevent  the  blood  in  the  abdominal  vessels  from  passing  in 
the  portal  vein  through  the  liver  in  normal  quantities,  so  that  a 
large  part  of  this  blood  escapes  the  customary  regulating  influence 
of  the  liver  by  being  made  to  pass  through  the  other  otherwise  com- 
paratively unimportant  channels  outside  the  liver.  Claude  Bernard 
thus  caused  glycosuria  in  the  dog  by  ligation  of  the  portal  vein. 
Andral,  as  early  as  1856,  found  sugar  in  the  urine  in  a  case  of  pyle- 
thrombosis,  and  Colrat  and  Couturier,  in  the  seventies,  confirmed 
this  observation. 

Finally,  we  may  not  unreasonably  assume  that  such  processes 
as  directly  decrease  the  power  of  the  liver  to  store  the  glycogen 
may  tend  to  produce  glycosuria,  and  some  facts  seem  to  corrobo- 
rate this.  The  retention  of  bile  speedily  empties  the  liver-cells  of 
their  glycogen  (Dastre  and  Arthur,  Hergenhahn),  and  Golowin 
found  glycosuria  after  closure  of  biliary  fistulae,  v.  Wittisch  after 
ligation  of  the  bile-ducts.  Tscherinow  observed  glycosuria  in  asso- 
ciation with  acute  yellow  atrophy  of  the  liver,  Schmitz  with  amyloid 
degeneration  of  the  liver,  Neusser  with  poisoning  by  phosphorus. 


50  DIABETES    MELLITUS    AND    GLYCOSURIA. 

(This  effect  of  phosphorus,  however,  seems,  according  to  BolHnger, 
Huber,  and  Miinzer,  to  be  rather  the  exception  than  the  rule.) 
Cirrhosis  of  the  hver  has  been  the  subject  of  many  investigations  in 
this  connection,  but  in  default  of  an  exact  expression  for  the  normal 
power  of  assimilation  and  of  any  considerable  number  of  perfectly 
uniform  researches,  and  on  account  of  the  frequency  of  excretion 
in  the  urine  of  small,  pathologic  amounts  of  glucose,  apart  from  dis- 
ease of  the  liver,  it  is  difficult  to  arrive  at  definite  conclusions.  I 
have  in  this  connection  observed  a  large  number  of  patients  with 
simple  atrophic  cirrhosis  and  some  with  hypertrophic  cirrhosis  of 
the  liver,  and  repeatedly  have  found  glycosuria,  and  sometimes  true 
diabetes.  On  the  other  hand,  I  have  seen  quite  a  considerable 
number  of  patients  in  a  far-advanced  state  of  cirrhosis  of  the  liver 
that  were  able  to  take  large  amounts  of  carbohydrates  without  de- 
veloping glycosuria,  and  I  was  for  a  long  time  unable  to  make  up 
my  mind  as  to  the  supposed  intimate  connections  between  cirrhosis 
of  the  liver  and  glycosuria.  Even  now  I  am  able  to  accept  such  a 
connection  rather  on  account  of  Naunyn's  figures  of  about  sixteen 
per  cent,  of  cirrhosis  of  the  liver  among  diabetic  patients  than  from 
my  own  experience. 

Naunyn's  observations  seem  to  confirm  Claude  Bernard's  opin- 
ion as  to  the  greater  frequency  of  glycosuria  in  cases  of  incipient 
than  in  those  of  advanced  cirrhosis.  One  sometimes,  however,  finds 
glycosuria  in  patients  with  most  pronounced  cirrhosis  of  the  liver. 

Toxic  glycosuria  arises  from  the  ingestion  of  various  substances, 
and  many  experiments  that  have  recently  been  made  seem  to  indi- 
cate that  almost  any  poisonous  substance  may  increase  the  amount 
of  sugar  in  the  blood  and  cause  glycosuria,  and  that  this  may  even 
result  through  substances  that  are  normally  present  in  the  blood,  if 
they  be  injected  or  ingested  in  abnormally  large  amounts. 

Except  in  the  cases  in  which  phloridzin  has  been  given,  and  in 
those  of  slow  asphyxiation,  the  glycosuria  that  results  from  poison- 
ing is  always  caused  by  hyperglycemia,  which  may  be  the  result  of  a 
toxic  influence  exerted  in  various  ways.  Such  an  occurrence  may  be 
brought  about  by  a  direct  effect  on  the  nervous  centers,  and  through 
them  on  the  vasomotor  nerves,  with  hyperemia  of  the  liver  and  in- 
creased production  of  sugar  ;  or  by  a  paresis  of  the  muscles,  with 


GLYCOSURIAS.  5 1 

decreased  consumption  of  the  sugar  of  the  blood,  either  in  conse- 
quence of  metabolic  changes  in  the  muscles  themselves,  or  in  con- 
sequence of  disturbances  of  respiration  and  want  of  oxidation  ;  or 
of  an  influence  on  the  tissues  and  on  cellular  vitality,  with  deteriora- 
tion of  the  general  metabolism  ;  or  of  some  influence  on  the  Hver- 
cells,  with  a  weakening  of  their  power  to  store  glycogen  ;  or  of  a 
change  in  the  epithelial  elements  of  the  kidneys,  in  consequence  of 
which  they  permit  the  escape  of  the  sugar  of  the  blood  with  the 
urine  (phloridzin).  We  have  as  yet  on  this  subject  only  hypotheses 
that  are  analogous  to  the  theories  concerning  diabetes.  An  enor- 
mous amount  of  experimental  work  will  be  required  to  put  us  in 
possession  of  all  the  knowledge  that  is  to  be  gained  from  a 
study  of  the  glycosuria  due  to  various  forms  of  poisoning. 

In  all  of  the  glycosurias  of  this  group,  with  the  exception  of 
that  due  to  phloridzin,  the  amount  of  sugar  in  the  urine  keeps  at  a 
moderate  level*  and  constitutes  only  an  unimportant  feature  of  the 
entire  clinical  picture.  Having  made  its  appearance  with  the  other 
symptoms,  the  glycosuria  generally  persists  for  some  time  after  the 
elimination  of  the  poison.  The  glucose  is  often  accompanied  by 
other  pathologic  substances.  One  of  these  is  lactic  acid,  which  is 
considered  to  represent  a  station  in  the  combustion  of  carbohy- 
drates on  their  way  to  complete  oxidation  and  to  the  formation  of 
carbonic  acid  and  water.  After  the  ingestion  of  chloralf  or  chloral- 
amid  (Manchot),  of  nitrobenzol  and  nitrotoluol  (Ewald,  v.  Mering, 
Magnus-Levy),  of  orthonitrophenyl-propionic  acid  (Hoppe-Seyler), 
side  by  side  with  the  glucose  we  find  the  combined  glycuronic 
acids,  which  reduce  solutions  of  copper  and  bismuth  and  deflect 
the  polarized  light  to  the  left,  but  do  not  undergo  fermentation 
(see  below). 

Acids,  both  without  and  within  the  organism,  seem  to  favor  the 


*  Araki  has  recently  induced  glycosuria  by  the  administration  of  veratrin,  morphin, 
cocain,  strychnin,  amyl  nitrate,  and  carbon  dioxid,  the  amount  of  sugar  in  the  urine 
reaching  four  per  cent.  There  was  often  albuminuria.  The  lactic  acid  in  the  urine 
reached  two  per  cent. 

f  Ewald  first  saw  reduction  after  ingestion  of  chloral,  and  attributed  it  to  glucose. 
Von  Mering,  however,  by  the  absence  of  fermentation,  demonstrated  the  reducing  sub- 
stance to  be  something  else  than  glucose.  It  was  found  to  be  a  combined  glycuronic 
acid  (urochloralic  acid).     In  some  cases  both  substances  are  present. 


52  DIABETES    MELLITUS    AND    GLYCOSURIA. 

molecular  construction  of  sugar  and  to  facilitate  the  transmutation 
of  glycogen  into  glucose,  just  as  alkalies  seem  to  have  the  opposite 
effect.*  If  acids  are  introduced  into  the  blood  for  some  time  and 
in  sufficient  quantities,  they  cause  emaciation,  anemia,  lowering  of 
temperature,  neuralgia,  paresis  and  paralysis,  and,  finally,  a  state 
that  greatly  resembles  diabetic  coma  (Rolf,  Walter,  Hugonenq, 
Stadelmann,  Kiilz,  and  others).  Moreover,  there  may  or  may  not 
be  albuminuria.  The  glycosuria  also  is  not  constant,  and  when  it 
follows,  it  is  slight.  It  has  been  observed  in  cases  of  poisoning 
with  sulphuric  acid  (Pavy),  lactic  acid  (Golz,  Naunyn),  hydrochloric 
acid  (Naunyn  and  others),  salicylic  acid  (PoUatschek),  prussic  acid 
(Geppert),  oxalic  acid,  orthonitrophenyl-propionic  acid  (Hoppe- 
Seyler),  and  the  lower  fatty  acids  (Mayer). 

Frerichs  reports  some  cases  of  poisoning  with  sulphuric  acid,  in  which  he 
found  sugar  in  the  urine  only  exceptionally,  though  reducing  substances, 
which  do  not  undergo  fermentation  (combined  glycuronic  acids),  are  not 
rarely  present. 

I.  B.  L.,  a  healthy  servant-girl  of  twenty-two,  took  a  large  quantity  of  con- 
centrated sulphuric  acid  and  excreted  as  much  as  0.5  per  cent,  of  glucose 
(reduction,  rotation,  fermentation).  The  ^specific  gravity  of  the  urine  was 
1.043,  ^'^d  rio  albumin  was  present. 

2.  M.  S.,  in  the  fifth  month  of  pregnancy,  drank,  on  May  26th,  concentrated 
sulphuric  acid ;  was  given  calcined  magnesia  in  milk,  but  vomited  blood ; 
had  violent  pains  in  the  mouth  and  throat,  hoarse  voice,  and  pain  in  the  epi- 

*  Acids  cause  saccharification  of  glycogen  and  starch,  while  alkalies  do  not.  Coignard 
watered  radishes,  Martin-Damourette  a  vine,  with  alkaline  water,  and  thus  obtained  a 
much  smaller  amount  of  sugar  in  the  roots  of  the  former  and  in  the  fruits  of  the  latter, 
than  by  using  ordinary  water.  Ehrlich  found  that  frogs  living  in  a  solution  of  glucose 
stored  a  good  deal  of  glycogen  in  their  livers  when  sodium  bicarbonate  was  added  to  the 
solution  of  glucose,  but  a  comparatively  small  amount  when  acetic  acid  was  added,  Pavy 
assumes  that  sulphuric  acid  injected  into  the  blood  favors  the  transmutation  of  glycogen 
in  the  liver  into  sugar,  but  that  injections  of  sodium  bicarbonate  favor  its  transmutation 
into  something  else.  His  opinion  that  the  latter-named  injections  decrease  the  hepatic 
glycogen  was  not  borne  out  by  the  experiments  of  Kiilz,  which  yielded  exactly  opposite 
results.  In  cases  of  severe  diabetes  with  large  quantities  of  (diacetic  and  /3-oxybutyric) 
acids  in  the  blood  the  hepatic  glycogen  is  distinctly  diminished  (Frerichs,  v.  Mering  and 
Mmkowski,  Stadelmann).  As  a  result  of  his  experiments  Kulz  reached  the  somewhat 
uncertain  conclusion  that  dextronic  acid,  sugar  acid,  and  mucous  acid  contribute  to  the 
formation  of  glycogen  in  the  liver.  This  seemed  certainly  to  be  the  case  with  the  an- 
hydrid  of  glycuronic  acid,  which  is  molecularly  closely  related  to  glucose.  Even  if  all 
these  weak  acids  should  in  some  way  contribute  to  the  formation  of  glycogen  in  the  liver, 
it  can  scarcely  be  doubted  that  stronger  acids  in  the  blood  are  decidedly  antagonistic  to 
such  a  result. 


GLYCOSURIAS.  53 

gastrium.  She  voided  700  cu.  cm.  urine  of  a  specific  gravity  of  1.045  (■)>  ^^^^ 
from  albumin,  sugar,  and  other  reducing  substances.  On  May  28th  the  spe- 
cific gravity  was  1.039,  ^^^  '^^^'^  ^^Y  ^-^S^'  ^^'^  ^^^^  from  abnormal  substances. 
On  June  1st  the  urine  had  a  specific  gravity  of  1.034,  was  dark,  smelt  of  ace- 
tone, and  yielded  a  wine-red  reaction  with  ferric  chlorid  (diacetic  acid  from 
inanition).  There  was  no  reduction,  no  rotation  of  the  polarized  light,  no 
albumin.  The  sulphuric  acid  present  in  the  urine  equaled  1.68  grams,  of  which 
1.43  were  mineral  sulphates  and  0.25  aromatic  sulphates.  Thus,  the  latter 
were  increased,  although  the  whole  amount  was  not  abnormal.  The  vomit- 
ing and  the  pains  continued,  so  that  only  small  quantities  of  liquid  food 
could  be  taken  during  the  first  few  days.  On  June  3d  the  patient  was  able 
to  take  more  food;  on  June  5th  the  wine-red  reaction  of  the  urine  had  dis- 
appeared, while  the  specific  gravity  was  i.oio,  and  the  sulphuric  acid  equaled 
1. 1 8  grams. 

It  has  been  proved  that  a  large  number  of  partly  indifferent, 
partly  poisonous,  metals  and  metallic  salts,  when  injected  into  the 
blood  or  taken  by  the  mouth,  are  capable  of  causing  glycosuria. 
This  is  the  case  with  injections  into  the  blood  of  ordinary  sea-salt 
(Bock  and  Hoffmann,  see  below),  sodium  bicarbonate  (Kiilz,  Kess- 
ler),  sodium  acetate,  sodium  valerianate,  sodium  succinate,  sodium 
phosphate,  and  sodium  sulphate  (Kiilz,  Kuntzel),  as  well  as  with 
sodium  salicylate  taken  by  the  mouth  (Burton). 

Phosphorus  (Bollinger,  Huber,  v.  Jaksch),  arsenic  (Bernard, 
Quinquaud,  Saikowski,  Masoin),  mercury  (Reynoso,  Rosenbach, 
Bouchard,  Cartier,  v.  Mering),  lead  (Brunelle,  Strauss),  uranium 
(Cartier),  also  cause  glycosuria  more  or  less  constantly. 

At  least  under  some  of  the  conditions  named  the  hypergly- 
cemia is  induced  through  the  agency  of  the  nerves,  as  glycosuria 
does  not  follow  the  injection  of  sea-salt  if  the  splanchnic  nerves  are 
divided  (Kiilz). 

Phosphorus  causes  glycosuria,  lactaciduria,  and  peptonuria,  but  none  of  these 
is  constant.  Von  Jaksch  observed  glycosuria  in  15  of  43  cases  of  phosphorus- 
poisoning.  Of  Miinzer's  ten  cases,  of  which  several  terminated  fatally,  it  is  in 
most  cases  especially  stated  that  the  urine  contained  no  sugar,  and  in  no  single 
case  is  it  mentioned  that  there  was  any.  Laub  in  two  cases  noted  0.15-0.7  per 
cent,  of  glucose.  Von  Jaksch  mentions  that  glycosuria  is  common  in  such 
cases  when  icterus  is  present. 

Arsenic,  which  has  the  power  of  preventing  glycosuria  after  Bernard's  punc- 
ture, and  is  used  therapeutically  because  of  its  property  of  diminishing  the  ex- 
cretion of  sugar  in  the  urine,  in  toxic  doses  sometimes  causes  glycosuria. 
Whether  this  is  a  consequence  of  the  glycogen  being  driven  out  of  the  liver 
and  the  muscles  being  unable  to  consume  the  increased  sugar  in  the  blood 


54  DIABETES    MELLITUS    AND    GLYCOSURIA. 

(Zimmer),  or  the  effect  of  the  accumulation  of  arsenic  in  the  brain  (Scolozoboff ), 
has  not  been  decided. 

Feilchenfeld  has  described  a  case  of  acute  arsenical  poisoning  with  an  ex- 
tensive, fully  developed,  multiple  neuritis.  The  case,  which  first  seemed  to  be 
one  of  true  diabetes  (4.7  per  cent,  of  sugar),  soon  settled  down  to  an  insignifi- 
cant glycosuria. 

Both  sugar  and  albumin  are  sometimes  found  in  the  urine  of  persons  under- 
going antisyphilitic  mercurial  treatment,  but  only  when  the  mercurial  poisoning 
is  pronounced  (Frerichs,  Kussmaul,  Lewin).  Graf  noticed  in  rabbits  constant 
glycosuria  after  doses  of  mercuric  chlorid. 

Brunelle  found  from  0.2  to  i  per  cent,  of  glucose  in  the  urine  after 
administration  of  200  grams  of  syrup  in  more  than  half  of  a  number  of  cases 
of  lead-poisoning. 

Uranium  and  its  salts  constantly  cause  glycosuria  and  albuminuria.* 
Those  that,  not  very  wisely,  have  introduced  uranium  nitrate  into  therapeutics 
for  the  purpose  of  diminishing  glycosuria,  should  have  first  considered  its 
poisonous  properties.  Cartier  found  subcutaneous  injections  of  from  _^  to  2 
milligrams  per  kilo  of  body  weight  to  be  fatal,  the  animals  (rabbits)  mani- 
festing thirst,  diarrhea  or  constipation,  loss'of  appetite,  somnolence,  torpor, 
paresis  or  paralysis,  retarded  respiration,  emaciation,  lowering  of  temperature, 
and  death  in  coma,  with  or  without  convulsions.  The  glycosuria  appeared  about 
twenty  minutes  after  the  injection,  reached  its  maximum  in  a  day  or  two,  seldom 
exceeded  more  than  i  per  cent,  of  sugar,  and  then  decreased.  The  urine  first 
increased,  then  decreased,  anuria  finally  setting  in.  Acetone  was  present, 
probably  from  inanition.  The  autopsy  disclosed  a  severe  congestion  of  the 
whole  gastrointestinal  tract,  with  ulcerations  in  the  stomach  and  the  duodenum. 
The  liver  was  intensely  hyperemic  ;  large  amounts  of  the  drug  caused  cellular 
necrosis.  The  kidneys  were  also  markedly  congested,  and  the  seat  of  diffuse 
parenchymatous  inflammation,  often  with  cellular  necrosis.  The  heart  pre- 
sented subendocardial  ecchymoses.  Neither  the  nervous  system  nor  the  pan- 
creas nor  the  lungs  presented  noticeable  changes. 

Alcohol,  which  in  small  amounts  increases  the  power  of  assimilat- 
ing carbohydrates,  has  in  large  amounts  the  opposite  effect.  Thus, 
the  diabetic  is,  after  generous  indulgence  in  alcohol,  found  to 
excrete  far  more  sugar  than  he  does  otherwise  with  the  same 
allowance  of  carbohydrates  in  his  diet.  Simple  glycosuria  may, 
under  the  same  influence,  be  attended  with  such  quantities  of  sugar 
in  the  urine  as  are  common  in  diabetes  ;  while  a  normal  individual 
may,  after  excesses  "in  Baccho,"  present  gl)xosuria.  This  effect 
is  more  easily  brought  about  in  some  persons  than  in  others,  but 

*  Glycosuria  following  the  ingestion  of  uranium  was  first  observed  by  Leconte  in  the 
beginning  of  the  fifties;  then  by  Gmelin,  Bernard,  Blake,  Rabuteau,  Curee,  Chittenden, 
Kowalewski,  Whitehouse,  Lambert,  Woroschilski,  and  Cartier. 


GLYCOSURIAS.  5  5 

probably  may  be  caused  in  any  individual — a  fact  well  worth  know- 
ing and  remembering,  to  avoid  false  diagnoses  of  diabetes.  Bever- 
ages that  contain  large  quantities  of  both  alcohol  and  carbohy- 
drates are  especially  efficient  in  causing  glycosuria,  which  is  often 
observed  after  indulgence  in  champagne  and  beer  and  also  in  that 
disgusting  mixture  of  arrack,  sugar,  and  water,  which  is  called 
Swedish  punch,  and  often  flows  too  freely  in  my  native  country. 
The  glycosuria  following  the  use  of  alcohol  is  generally  moderate, 
and  the  sugar  in  the  urine  keeps  within  one  per  cent.,  but  after 
excessive  indulgence  may  continue  for  several  days,  especially 
appearing  after  meals. 

In  cases  of  chronic  alcoholism  one  also  sometimes  finds  a  small 
amount  of  sugar  in  the  urine.  I  have,  however,  seen  a  consider- 
able number  of  such  persons  with  a  normal  power  of  assimilating 
carbohydrates. 

Ether,  now  and  again,  causes  glycosuria,  whether  injected  in  the  veins 
(especially  the  portal  vein,  Harley),  inhaled,  or  taken  by  the  mouth.  There 
are,  however,  individuals  that,  in  spite  of  long  and  great  abuse  of  ether, 
exhibit  no  glycosuria  (Frerichs).  Andral  observed  diabetes  in  such  a  case,  but 
the  question  whether  ^^j/ or  ^r^//<?^  remains  undecided. 

Chloroform  often  causes  the  excretion  of  small  amounts  of  sugar  (Eulen- 
burg  and  others). 

Chloral  csMse.?,  the  appearance  in  the  urine  of  urochloralic  acid,  belonging  to 
the  group  of  combined  glycuronic  acids  (v.  Mering) ;  on  account  of  its  reducing 
properties  this  acid  has  often  been  mistaken  for  glucose.  Chloral,  however, 
now  and  again  also  causes  true  glycosuria  (Telz,  Ritter,  Eckhard).  Manchot 
observed  slight  glycosuria  in  about  one-fourth  of  a  number  of  cases  in  which 
chloralamid  was  being  administered. 

Amyl nitrite^  causes  glycosuria  more  surely  than  alcohol,  ether,  chloroform, 
or  chloral,  the  sugar  in  the  urine  rising  at  times  above  two  per  cent.,  and 
appearing  for  twenty-four  hours  after  inhalation  (Fr,  A.  Hoffmann).  Bouchard 
thinks  this  due  to  the  transmutation  of  the  oxyhemoglobin  into  methemoglobin 
and  to  deficient  oxidation;  others  lay  stress  on  the  vasoparalytic  influence  and 
the  congestion  of  the  liver. 

Lactic  acid  is  under  these  circumstances,  as  under  others,  sometimes  found 
in  the  urine  in  association  with  glucose. 

Ammonia,  when  injected  into  the  portal  vein,  causes  glycosuria,  which  also 
Bouchard  ascribes  to  the  decreased  capacity  of  the  blood  to  absorb  oxygen. 

Glycosuria  from  Asphyxia. — As  early  as  1868  Senator,  in  the 
course  of  his  investigations  on  the  effects  of  disturbed   respiration, 

*Siebold,  "  Ueber  d.  Amylnitrit-Diabetes,"  Diss.,  Marburg,  1S74. 


56  DIABETES    MELLITUS    AND   GLYCOSURIA. 

found  glycosuria  to  be  one  of  these  effects,  although  it  proved 
subsequently,  after  continued  clinical  observation,  to  be  the  excep- 
tion rather  than  the  rule. 

Senff  in  1869  observed  that  dogs,  after  inhaling  carbonic  acid, 
constantly  exhibited  glycosuria,  sometimes  accompanied  by  albumi- 
nuria. He  found  hyperglycemia,  but  a  normal  capacity  on  the 
part  of  the  muscles  to  consume  sugar,  and  he  therefore  attributed 
the  hyperglycemia  to  an  increased  production  of  sugar  in  the 
liver. 

Dastre  in  1879,  i^  ^i^  thesis  "  Sur  la  Glycaemie  Asphyctique," 
made  a  distinction  between  slow  and  rapid  asphyxiation  :  the  former 
causing  hypoglycemia,  the  latter  hyperglycemia,  and  both,  glycosu- 
ria. In  slow  asphyxiation,  when  the  animals  breathed  in  closed 
compartments  or  in  rarefied  air,  the  amount  of  sugar  in  the  blood 
was  distinctly  diminished,  and  Dastre  attributes  the  glycosuria 
under  these  conditions  to  the  want  of  oxygen  and  the  greatly  re- 
duced oxidation,  in  consequence  of  which  even  the  decreased 
amount  of  sugar  in  the  blood  is  not  consumed. 

In  the  nineties  Hoppe-Seyler's  pupils— Araki,  Zillesen,  and 
Irisawa — proved  that  different  conditions  and  circumstances  that 
induce  dyspnea  or  are  attended  with  a  deficiency  in  the  supply 
of  oxygen  (agony,  severe  anemia,  etc.),  often  also  cause  glucose 
and  lactic  acid  to  appear  in  the  urine,  though  neither  the  one  nor 
the  other  is  always  present. 

Hoppe-Seyler's  pupils  consider  the  glycosuria  attending  the  col- 
lapse due  to  many  poisons  (curare,  delphinin,  strychnin,  morphin, 
chloroform,  ether,  sulphonal,  carbonic  acid,  hydrocyanic  acid,  etc.), 
as  well  as  that  appearing  during  tetanus,  after  epileptic  attacks  and 
other  similar  states,  as  being  of  asphyctic  type.  Schiff,  Sauer,  and 
others  also  insist  that  the  glycosuria  does  not  appear,  or  that  it 
disappears,  if  asphyxia  is  prevented  by  proper  artificial  respiration. 
Still  there  are  other  plausible  explanations  :  Dastre  is  of  opinion 
that  asphyctic  blood  excites  the  liver  to  increased  production 
of  sugar,  and  remarks  that  the  glycosuria  due  to  many  poisons 
appears  before  any  deficiency  of  oxidation  could  be  effective. 

Glycosuria  due  to  carbon  monoxid  was  mentioned  by  Bernard 
(1857),  investigated  by  Senff  (1869),  and  afterward  studied  by 
Richardson,  Ollivier,  Biefel  and  Pollek,  Frerichs,  Hasse,  Kahler, 


GLYCOSURIAS.  57 

V,  Jaksch,  Araki,  Garofalo,  Rosenstein,  Walter  Straub,  Vamossy, 
and  others.  It  is  caused  by  hyperglycemia  ;  the  sugar  in  the  urine 
may  reach  1.5  per  cent,  in  man  (Frerichs)  and  4  per  cent,  in  the 
dog  (Senff).  Lactic  acid  injected  subcutaneously  reappears  almost 
entirely  in  the  urine,  but  sugar  injected  does  not.  In  fact,  Walter 
Straub,  Rosenstein,  and  Vamossy  all  have  arrived  at  the  conclusion 
that  the  amount  of  glucose  in  the  urine  in  this  most  remarkable 
kind  of  glycosuria  is  not  increased  by  the  ingestion  of  sugar,  and 
that  the  glucose  is  not  derived  from  carbohydrates,  but  from  pro- 
teids,  especially  fibrin  (Vamossy). 

Curare  causes  glycosuria,  as  was  known  to  Bernard,  and  the  condition 
has  since  been  made  the  subject  of  many  investigations.*  The  glycosuria 
appears  quickly,  and  is  associated  not  only  with  polyuria,  but  also  with  hyper- 
secretion of  the  sudoriparous,  salivary,  lacrimal,  and  intestinal  glands.  The 
abdominal  organs,  especially  the  liver,  are  intensely  hyperemic.  Langendorff 
maintains  that  extirpation  of  the  liver  does  not  prevent  the  glycosuria  due  to 
curare,  although  starvation  does.  Unlike  what  takes  place  in  the  glycosuria 
due  to  strychnin,  the  liver  afterward  may  contain  a  considerable  amount  of 
glycogen.  Schiff,  Penzoldt,  Fleischer,  Zuntz,  and  Sauer  agree  as  to  the  free- 
dom of  the  urine  from  sugar,  if  artificial  respiration  is  properly  maintained. 
As  long  as  this  is  successful,  the  urine  contains  a  reducing,  but  not  a  ferment- 
ing, substance  (probably  pyrocatechin,  Sauer),  but  as  soon  as  respiration  begins 
to  fail  sugar  appears.*  The  glycosuria  due  to  methyl  delphinin  seems  to  be 
very  like  that  due  to  curare. 

Glycosuria  due  to  strychnin  was  observed  in  the  fifties  by  Claude  Bernard 
and  by  Schiff;  it  was  afterward  studied  by  Langendorff  and  by  Giirtler.  It  is 
most  easily  induced  in  frogs  in  the  autumn,  when  their  livers  are  well  stored 
with  glycogen.  The  sugar  is  somewhat  slow  to  appear,  and  may  not  do  so  for 
a  whole  day.  It  may  then  persist  for  several  days,  although  at  a  low  figure. 
The  liver  is  emptied  of  its  glycogen  (the  "paraplasma"  or  substratum,  for  it  is 
diminished),  and  the  hepatic  cells  are  reduced  in  size  and  become  polygonal 
in  shape  (Langendorff).  Extirpation  of  the  liver  prevents  the  development  of 
the  glycosuria,  as  does  also  destruction  of  the  spinal  cord,  while  severance  of 
the  head  from  the  body  does  not  (Claude  Bernard).  The  glycosuria  does  not 
depend  on  the  tetanus,  as  it  appears  also  if  the  muscles  are  entirely  paralyzed. 
There  is  sortie  polyuria  and  lactaciduria. 

Morphin  gives  rise  to  glycosuria,  as  is  well  known  from  Eckhard's  work,  and 
as  can  easily  be  demonstrated  by  injecting  from  three  to  five  centigrams 
of  the  sulphate  or  hydrochlorate  subcutaneously  in  a  rabbit.  The  sugar  ap- 
pears in  small  quantities  as  early  as  the  second  hour  after  the  injection,  and 
often  persists  only  for  a  i^^N  hours  ;  the  condition  is  the  result  of  hyperglyce- 

*  Winogradoff,  Casal,  Lionville,  Langendorff,  Voisin,  Saikowski,  Schiff,  Doch,  Gag- 
lio,  Demant,  Penzoldt  and  Fleischer,  Zuntz,  Sauer  ("  Pfliiger's  Archiv,"  1S91). 
5 


58  DIABETES    MELLITUS    AND    GLYCOSURIA. 

mia  (Seegen).  Like  the  glycosuria  after  Bernard's  puncture,  that  due  to  mor- 
phin  is  prevented  not  by  section  of  the  pneumogastric,  but  by  that  of  the 
splanchnic  nerves  or  of  the  spinal  cord  above  the  roots  of  these  nerves.  After 
large  doses  the  transitory  polyuria  is  followed  by  a  decreased  secretion  or  even 
by  anuria.  An  injection  of  glycerin  prevents  the  glycosuria  (Luchsinger),  or 
at  least  has  an  effect  in  that  direction  (Eckhard). 

Sugar  is  sometimes  found  in  the  urine  of  morphinists  and  sometimes  not 
(Pichon).  I  have  found  only  slight  traces  in  a  few  cases  of  this  kind.  In  these, 
as  in  other  cases  of  poisoning,  the  acute  state  is  attended  with  more  pro- 
nounced glycosuria,  and  more  frequently,  than  the  chronic  state. 

Veratrin  causes  slight  glycosuria  and  lactaciduria  (Araki) — not  in  conse- 
quence of  diminished  "  glycolytic  power  "  on  the  part  of  the  blood,  but  on  ac- 
count of  an  increased  production  of  sugar,  according  to  Lepine. 

Von  Noorden  observed  glycosuria  after  the  use  of  ergotin. 

Many  diuretics  cause  glycosuria.  This  and  some  other  facts  have  of  late  led 
some  observers  to  the  conclusion  that  there  is  a  glycosuria  due  to  polyuria. 
When  Bock  and  Hoffmann  injected  a  one  per  cent,  solution  of  sodium 
chlorid  into  the  veins  of  the  rabbit,  the  animals  first  presented  distinct  poly- 
uria and  later  glycosuria.*  Jacoby  (Strassburg)  found  that  sulphocaffeinic 
acid,  sodium  caffein,  benzoate,  and  theobromin-sodium  salicylate  ("  diuretin  "), 
all  diuretics,  caused  glycosuria.! 

Klemperer,  who  strongly  maintains  that  glycosuria  may  result  from  poly- 
uria, found  sugar  after  administration  of  digitalis.  We  often  find  inosite  ac- 
companying polyuria — why  not  also  glucose  ?  There  are  also,  at  times,  cases 
of  diabetes  insipidus  with  traces  of  glucose  in  the  urine — though  this  does  not 
at  all  seem  to  be  a  common  occurrence.  It  is  not  easy  to  make  up  one's  mind 
definitely  as  to  the  glycosuria  resulting  from  polyuria.  The  facts  already 
mentioned  may  be  explained  in  different  ways,  and  there  is  one  important  and 
well-known  fact  that  denotes  that  polyuria  does  not  always  produce  glycosu- 
ria. Cirrhosis  of  the  kidneys  is  attended  with  polyuria,  but  not  with  glycosu- 
ria, and  in  case  of  diabetes  it  has  a  decided  influence  in  decreasing  the 
glycosuria. 

Some  animal  poisons  cause  glycosuria.  Ewald,  and  afterward  Strauss,  found 
as  much  as  six  per  cent,  of  glucose  in  the  urine  after  administration  of  thy- 
roidin  ;  when  the  thyroidin  ceased,  the  glycosuria  also  ceased. 

Teschemacher  noted  glycosuria  after  injections  of  Koch's  tuberculin; 
Dufresne,  after  injections  oi  pancreatin. 

Toepfer  and  Freund  observed  glucose  after  injections  of  a  dialysate  of 
feces.     The  fact  that  the  glycosuria  reached  a  greater  intensity  and  was  of 

*  This  experiment,  however,  has  many  other  effects  than  polyuria,  and  especially  a 
decrease  in  the  glycogen  in  the  liver,  and  hyperglycemia.  In  some  cases  there  was  also 
albumin  and  even  blood  in  the  urine,  denoting  a  condition  of  the  kidneys  that  by  some 
persons  is  considered  conducive  to  glycosuria. 

•f-  Neumann  administered  "  diuretin  "  in  a  case  of  insufficiency  of  the  aortic  valve,  and 
observed  polyuria  and  glycosuria,  which  he  ascribes  to  the  heart-disease.  The  glyco- 
suria may  as  well  have  been  caused  by  the  "diuretin." 


GLYCOSURIAS.  59 

longer  duration  when  feces  from  diabetics  were  used  than  when  the  feces  were 
derived  from  healthy  individuals,  may,  if  not  dependent  on  mere  chance,  be 
explained  by  the  customary  greater  abundance  of  the  products  of  the  putre- 
faction of  proteids  in  the  intestines  of  diabetics.  The  theory  advanced  by 
Toepfer  belongs,  in  my  opinion,  to  what  Punch  calls  "things  one  would 
rather  have  left  unsaid." 

As  is  well  known,  the  liver  is  supposed,  among  other  functions,  to  have  that 
of  retaining  poisonous  substances  absorbed  from  the  alimentary  canal  and  of 
preventing  their  entrance  into  the  blood.  On  the  other  hand,  the  toxicity  of 
the  urine  is  an  index  of  the  amount  of  such  substances  in  the  blood.  Roger 
("Action  d.  Foie  sur  les  Poisons,"  Paris,  1887)  observed  that  patients  suffering 
from  various  hepatic  disorders  and  secreting  a  highly  poisonous  urine  readily 
developed  glycosuria  after  the  ingestion  of  considerable  amounts  of  sugar;  and 
he  expresses  the  opinion  that  the  liver  has  in  those  cases  lost  in  part  its  capacity 
for  retaining  the  poisons  and  for  converting  alimentary  sugar  into  glycogen. 

Phloridsin-glycosiiria. — Scarcely  had  Koninck  (1885)  discovered 
phloridzin  when  v.  Mering  (1886)  observed  that  this  substance 
causes  an  exceedingly  peculiar  form  of  glycosuria. 

Phloridzin  is  a  glucosid  obtained  from  the  bark  of  the  root  of 
certain  species  of  Pyrus  and  Prunus.  It  crystallizes  in  glistening 
silky  crystals  and  is  easily  soluble  in  warm  water,  but  requires  1000 
parts  of  cold  water  for  its  solution.  Phloridzin  is  levogyrate.  It  is 
decomposed  by  boiling  with  diluted  acids  : 

Phloridzin  X  Water  =  Plilorose  +  Phloretin. 

Phlorose,  as  will  be  seen,  is  a  hexose,  has  the  same  molecular 
construction  as  glucose,  which  it  resembles  greatly,  is  dextrogyrate, 
and  reduces,  though  in  less  degree  than  glucose. 

Phloretin,  though  less  efficient  in  this  respect  than  phloridzin,  also 
causes  abundant  glycosuria.  Treated  with  caustic  alkali,  it  forms 
phloretic  acid  (an  aromatic  alcoholic  acid)  and  phloroglucin  (a  tri- 
atomic  aromatic  alcohol),  both  of  which  are  probably  also  formed 
in  the  organisms  ;  they  do  not  cause  glycosuria,  but  increase  the 
combined  aromatic  sulphatic  acids  in  the  urine  (Moritz  and  Prauss- 
nitz).  In  the  course  of  the  intoxication,  and  as  long  as  the  glyco- 
suria lasts,  there  appears  in  the  urine  a  brownish-violet  coloration 
on  addition  of  ferric  perchlorid  (due  to  phloridzin).  With  phlore- 
tin a  similar,  but  more  deeply  violet,  reaction  is  obtained.  The 
urine,  especially  if  the  animal  has  been  kept  fasting,  becomes 
shghtly  albuminous. 


60  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  glycosuria  commences  after  a  couple  of  hours,  after  o.oi 
gram  per  kilo  of  body  weight  has  been  given  by  subcutaneous  injec- 
tion, and  after  double  that  dose  by  the  mouth  in  dogs.  After  large 
doses  the  amount  of  sugar  may  rise  to  more  than  thirteen  per 
cent.  (Moritz  and  Praussnitz),  or  even  to  more  than  eighteen  per 
cent.  (v.  Mering)  in  dogs,  and  it  may  persist  for  several  days  or  a 
week  (Coolen).  The  quantity  of  urine  is  not  increased,  but  the 
specific  gravity  may  rise  to  1.070.  In  rabbits  the  glycosuria  is 
less  marked  and  more  transitory,  but  it  appears  regularly  after 
subcutaneous  injections  ;  after  injection  of  two  grams  it  persists  for 
from  seven  to  twenty  hours  (Lusk).  It  is  also  observed  in  the 
hen,  the  goose,  and  the  frog  (Ritter  and  Cremer).  It  has  been 
observed  in  the  goose  after  extirpation  of  the  liver  (v.  Mering, 
Thiel). 

The  organism,  even  under  the  influence  of  phloridzin,  assimilates 
a  considerable  part  of  the  ingested  carbohydrates.  The  larger  the 
dose  of  phloridzin,  the  greater  the  absolute  value  of  the  sugar  in 
the  urine,  but  the  smaller  its  value  in  relation  to  the  dose. 

Klemperer,  and  recently  (1899)  Achard  and  Delamare,  have 
found  phloridzin  to  give  rise  to  much  less  marked  glycosuria  in 
cases  of  chronic  nephritis  than  otherwise. 

Phloridzin,  as  may  be  understood  from  the  relation  between  the 
quantity  ingested  and  the  amount  of  sugar  in  the  urine,  acts  in  a 
"  specific  "  manner,  and  not  by  reason  of  being  a  glucosid,  as  other 
glucosids  do  not  cause  glycosuria  (v.  Mering,  Gley,  Germain  See). 
Thus,  6  grams  of  phloridzin,  containing  2.5  grams  of  phlorose, 
may  cause  glycosuria  with  41.7  grams  of  sugar  in  the  urine. 

An  abundant  mixed  diet,  including  a  great  deal  of  sugar  and 
starch,  causes  the  glycosuria  to  reach  its  maximum  ;  but  it  continues 
during  starvation  and  even  after  extirpation  of  the  liver.  Von  Mering 
found  glycosuria  in  the  dog  when  the  liver  and  the  muscles  were 
almost,  but,  as  Kiilz  remarks,  not  completely,  emptied  of  glycogen. 

When  the  food  is  made  up  exclusively  of  fat,  the  glycosuria  falls 
as  low  as  in  starvation  (v.  Mering,  Moritz,  and  Praussnitz) — a  most 
remarkable  circumstance,  which  speaks  against  the  opinion  of  those 
who  think  that  fat  may,  with  a  deficiency  of  carbohydrates  and 
of  albumin,  form  glucose  in  the  organism. 

As  long  as  the  food  is  abundant  enough  to  cover  the  heat-wants 


GLYCOSURIAS.  6 1 

of  the  organism  and  the  loss  of  sugar  in  the  urine,  even  large  doses 
of  phloridzin  do  not  cause  any  general  disturbances  ;  but  during 
starvation  and  poisoning  with  phloridzin  inanition  speedily  develops  ; 
the  animals  quickly  lose  weight ;  the  proteids  of  the  organism  are 
decomposed;  acetone,  diacetic  acid,  and  /'J-oxybutyric  acid  show  them- 
selves in  the  urine,  while  the  ammonia  increases,  and  weakness  and 
somnolence  become  manifest.  If  the  animals  are  then  killed,  the 
liver  and  the  muscles  are  found  in  a  state  of  fatty  degeneration. 
[Rosenfeld  is  of  the  opinion  that  the  fat  in  the  liver  in  these  cases 
is  derived  from  an  infiltration  of  fat  from  other  parts  than  the  liver, 
and  not  from  fatty  degeneration  of  proteids  in  the  liver-cells.]  If 
the  animals  are  given  food  and  the  phloridzin  is  withheld,  they 
speedily  return  to  health.  The  liver  is  said  to  store  more  glycogen 
from  meat  under  the  influence  of  phloridzin  than  if  the  animals 
receive  only  sugar. 

The  most  peculiar  feature  of  the  phloridzin  glycosuria,  however, 
is  the  presence  of  a  decreased  percentage  of  sugar  in  the  blood. 
Von  Mering  and  almost  all  other  observers  agree  on  this  point.* 

Von  Mering  found  from  0.075  to  0.09  per  cent,  of  sugar  in  the 
blood  with  from  6.5  to  9.2  per  cent,  of  sugar  in  the  urine  of  the 
dog,  the  blood  normally  containing  about  o.  10  per  cent.  Gabrit- 
schewski  found  that,  while  the  white  corpuscles  of  hyperglycemic 
(diabetic)  blood  contain  an  abnormally  large  quantity  of  glycogen, 
they  contain  an  unusually  small  amount  thereof  in  phloridzin  cases. 

There  are  only  two  ways  of  explaining  phloridzin-glycosuria — it 
may  arise  in  consequence  of  some  alteration  in  the  epithelial  ele- 
ments of  the  kidneys  (v.  Mering),  or  it  may  be  the  result  of  some 
combination  of  phloridzin  or  one  of  its  derivatives  with  glucose 
(Graham,  Lusk).  In  either  case  the  passage  of  the  latter  into  the 
urine  is  facilitated,  and  the  blood,  the  liver,  the  muscles,  and  the 
whole  organism  are  thus  deprived  of  both  sugar  and  glycogen, 
which  are  constantly  renewed,  though  not  at  the  same  rate  as  they 
are  lost. 

After  extirpation   of  the  kidneys  the  hypoglycemia  ceases,  but 

*  Pavy,  whose  researches  on  blood-sugar  have  led  him  to  such  curious  conclusions, 
has  not  found  any  hypoglycemia  during  phloridzin-glycosuria  ("  Journ.  of  Physiol.," 
London,  1894).  Coolen  also  found  no  decrease  of  blood-sugar,  and  Levene  found  a 
somewhat  higher  figure  for  the  sugar  in  the  renal  vein  than  in  the  arterial  system. 


62  DIABETES    MELLITUS    AND    GLYCOSURIA. 

hyperglycemia  does  not  arise.  Zuntz  took  the  urine  from  both 
ureters  of  the  dog  immediately  after  an  injection  of  phloridzin  into 
one  of  the  renal  arteries,  and  found  that  the  urine  on  this  side 
immediately  became  sacchariferous,  while  that  on  the  other  side 
became  so  only  when  the  phloridzin  had  reached  the  kidney  on 
this  latter  side  through  the  entire  circulatory  system. 

According  to  Cornevin,  phloridzin  has  an  analogous  influence  on 
the  lactogenous  glands  and  increases  the  lactose  in  the  milk. 

Antipyrin  (See  and  Gley)  and  syzygium  jambolanum  (Graser) 
act  in  a  manner  opposite  to  phloridzin,  and  diminish  the  glycosuria. 

Phloridzin  and  phloretin  are  sometimes  used  for  the  purpose  of 
simulating  diabetes. 

The  glycosuria  due  to  infectious  diseases  is  generally  attended  with 
the  presence  of  insignificant  quantities  of  sugar  in  the  urine,  and 
occurs  very  inconstantly  in  the  course  of  acute  exanthematous  and 
other  infections.  It  is  not  yet  known  under  what  conditions  and 
during  which  period  the  sugar  appears.  On  the  one  hand,  we 
know  positively  that  the  sugar  in  the  urine  in  diabetes  or  glyco- 
suria decreases  and  sometimes  disappears  during  the  febrile  state, 
while,  on  the  other  hand,  the  infectious  diseases  attended  with  fever 
often  induce  glycosuria.  Poli  recently,  after  the  administration  of 
glucose  in  cases  of  scarlet  fever,  diphtheria,  septicemia,  tonsillitis, 
and  pneumonia,  found  a  decreased  power  of  assimilation  and  a 
much  greater  portion  of  the  ingested  glucose  in  the  urine  than 
would  have  appeared  in  normal  individuals.  In  cases  of  malignant 
pustule  Roger  found  the  sugar  in  the  blood  in  the  beginning  of  the 
disease  normal,  or  even  somewhat  below  the  customar)^  amount ; 
then  a  moderate  hyperglycemia,  with  from  0.22  to  0.30  per  cent,  of 
sugar  in  the  blood  appeared,  and  after  death  the  liver  contained  no 
glycogen.  In  other  cases  of  febrile  disease  the  glycosuria  appears 
during  the  period  of  defervescence  and  the  beginning  of  the  con- 
valescence. I  have  also  seen  it  during  the  prodromal  stage,  and  it 
does  not  seem  to  be  excluded  from  any  stage  of  febrile  infections. 

Glycosuria  is  often  found  in  the  course  of,  and  after,  influenza 
and  malaria ;  and  it  is  also  observed  in  the  course  of  typhoid  fever 
(Seyfert,  Bordier),  diphtheria  (Frerichs),  scarlet  fever  (Redon, 
Zinn),  measles  (Fischer,  Bouchut,  Bordier,  Barlow,  Gelmo),  dysen- 


GLYCOSURIAS.  63 

tery  (Anstoots),  cholera  (Heintz,  Samoje,  Huppert,  Gubler,  v. 
Terray,  Vas,  and  Gara),  croup,  pertussis,  pneumonia  (Bordier, 
Semmola,  Stern,  Beale,  Reynoso),  erythema  nodosum  (Bordier), 
variola,  and  vaccinia  (during  the  florid  stage,  Gueneau,  Prevost), 
anthrax  (Proust,  Philipeaux,  Vulpian,  Charcot,  Frerichs,  Goolden), 
lyssa  (Eichhorst),  lymphangitis,  and  erysipelas  (Redard),  and  septic 
processes  (Poli). 

It  would  seem  as  if  all  suppurative  processes  might  induce  glyco- 
suria, which  has  several  times  been  observed  in  association  with 
gangrene,  phlegmon,  noma,  and  especially  with  furunculosis  and 
carbuncle.  Wagner  was,  I  believe,  the  first  to  mention  glycosuria  as 
complicating  these  two  latter  skin  diseases.  Still,  as  is  well  known, 
furuncles  and  carbuncles  are  common  manifestations  of  diabetes. 
Furuncles  especially  appear  at  an  early  stage  of  the  dystrophy,  and 
there  still  remains  some  doubt  if,  in  the  cases  in  which  they  have 
been  considered  to  be  the  cause  of  glycosuria,  they  have  not  really 
been  the  effect  of  a  mild  diabetes. 

In  rare  cases  syphilis  causes  glycosuria  or  real  diabetes  by  attack- 
ing either  of  the  organs  that  preside  over  the  metabolism  of  carbo- 
hydrates. In  most  such  cases  arteriosclerosis,  cerebral  softening, 
hemorrhage,  or  gummata  in  the  brain  precede  the  appearance  of 
the  glycosuria.  The  few  cases  that  I  have  seen  were  examples  of 
glycosuria  or  mild  diabetes.  Sometimes  their  syphilitic  nature  be- 
comes apparent  e  jjivantibtis,  and  quite  a  number  are  recorded  of 
cure  by  antisyphilitic  treatment.  Decker  has  reported  such  a  case 
in  which  the  sugar  appeared  a  little  more  than  a  year  after  the  in- 
fection. Whether  syphilis  can  cause  glycosuria  in  any  other  way 
than  through  lesions  of  the  brain,  the  liver,  or  the  pancreas,  is  not 
known.* 

The  prognosis  of  glycosuria  (or  diabetes)  due  to  infectious  dis- 
ease is  decidedly  more  favorable  than  that  due  to  any  other  cause — 
the  sugar  generally  disappearing  from  the  urine  after  or  during  con- 
valescence. On  the  other  hand,  some  infections  undoubtedly  may 
lead  to  true  diabetes  ;  but  even  in  such   cases  one  may  sometimes 

*  One  writer  has  affirmed — in  a  book  and  in  advertisements  on  the  walls  in  Carlsbad — 
that  he  acres  diabetes,  which  he  considers  almost  always  to  be  an  effect  of  syphilitic  in- 
fection, either  acquired  or  inherited,  perhaps  from  some  ancestor  of  the  dark  ages.  Such 
a  statement  must  not  be  taken  too  seriously — quid  verbis  affirtnat  satis  est  verbis  negare. 


64  DIABETES    MELLITUS    AND    GLYCOSURIA. 

observe  instances  of  perfect  recovery.  I  have  seen  this  take  place 
after  typhoid  fever  and  after  influenza,  and  Zinn  mentions  a  similar 
occurrence  after  scarlet  fever,  and  Burdel  in  three  cases  after 
malarial  fever. 

In  cases  of  cholera  the  sugar  appears  chiefly  in  the  abundant  urine  follow- 
ing the  anuria  ;  it  is  often  accompanied  by  indoxyl  and  albumin ;  the  sugar 
rarely  amounts  to  one  per  cent,  and  disappears  during  the  first  days  of  conva- 
lescence. Cases  of  true  and  even  of  severe  diabetes  are  also  observed  in  con- 
nection with  cholera  (Frerichs) ;  but  sugar  is  far  from  being  found  in  all  cases. 
Von  Terray,  Vas,  and  Gara  found  it  only  in  one  case  of  sixteen  ;  the  glyco- 
suria began  twelve  days  after  the  end  of  the  anuria  ;  the  sugar  rose  to  0.5  per 
cent,  and  persisted  for  three  days.  The  urine  of  several  other  patients 
strongly  reduced  copper,  but  did  not  deflect  the  ray  of  polarized  light,  and  did 
not  undergo  fermentation. 

In  cases  of  typhoid  fever'xi  seems  that  sugar  may  appear  in  the  urine  as  early 
as  during  the  prodromal  period.  A  clergyman  came  to  Carlsbad  for  some  dys- 
peptic trouble,  and  presented  slight  evening  elevation  of  temperature  and  felt 
generally  ill.  A  dull  note  on  percussion  over  the  apex  of  the  left  lung  led  me  to 
suspect  an  incipient  tuberculosis.  A  large  specimen  of  urine  was  found  to 
contain  i.i  per  cent,  of  glucose.  I  quickly  sent  the  patient  to  his  home,  where 
the  typical  temperature-curve  of  typhoid  fever  developed.  After  the  end  of 
the  typhoid  (or  before)  the  glycosuria  disappeared. 

Malaria  is  not  rarely  accompanied  by  transitory  glycosuria,  which  comes 
on  after  every  paroxysm  and  sometimes,  though  rarely,  may  develop  into  true 
diabetes.*  The  glycosuria  diminishes  or  disappears  under  the  influence  of 
quinin.  Burdel  found  sugar  in  14  per  cent,  of  cases  of  quartan  or  tertian 
type,  in  22  per  cent,  of  cases  of  quotidian  type,  in  28  per  cent,  of  cases  of  per- 
nicious malaria,  and  in  80  per  cent,  of  cases  of  malarial  cachexia.  He  has 
recorded  three  cases  of  a  distinctly  diabetic  nature,  in  which  perfect  recovery 
ensued  after  the  use  of  quinin. 

Since  influenza,  in  the  beginning  of  the  nineties,  again  invaded  the  civilized 
world  there  have  been  published  many  observations  of  glycosuria  or  diabetes 
arising  in  the  course  of  this  disease,  really  much  more  dreadful  than  dreaded, 
I  have  myself  seen  all  forms  of  defective  power  of  assimilating  carbohydrates 
during  and  after  an  attack  of  influenza,  most  of  the  cases  presenting  slight 
degrees  of  glycosuria.  In  other  cases  of  simple  glycosuria  that  I  have  had 
under  observation  for  many  years,  repeated  and  severe  attacks  of  influenza 
have  been  without  any  effect  whatever  on  the  glycosuria.  I  have  seen  several 
cases  of  diabetes  following  influenza  improve  greatly  after  convalescence  from 

*  Peter  Frank  and  Sydenham,  more  than  a  century  ago,  mentioned  diabetes  in  con- 
nection with  malaria.  Burdel,  in  1859,  directed  the  attention  of  the  profession  to  the 
small  quantities  of  sugar  in  the  urine  of  patients  suffering  from  malaria.  Several  French 
physicians  in  North  Africa  (Calmette,  Rang6,  Duponchet)  have  contributed  to  the  litera- 
ture on  this  subject.  In  "  Malaria  and  Diabetes,"  Diss.,  Rostock,  1896,  Otto  Jacobson 
gives  the  bibliography. 


GLYCOSURIAS.  65 

the  causal  disease,  and  I  have  seen  at  least  one  case  in  which  perfect  recovery- 
ensued. 

Mr.  X.,  a  Finlander,  some  thirty  years  old,  came  in  June,  1890,  to  Carls- 
bad, having  had  his  first  attack  of  influenza  half  a  year  before.  In  February 
he  had  had  another  severe  attack,  with  high  fever,  violent  pains  in  the  back 
and  legs,  and  great  prostration.  Early  during  convalescence  the  patient  began 
all  at  once,  on  a  certain  day,  to  drink  and  to  urinate  freely,  and  an  apothecary 
found  in  the  urine  a  large  amount  of  glucose,  which  by  a  specialist  was  esti- 
mated at  8.8  per  cent.  Unfortunately,  I  could  obtain  no  information  as  to 
whether  any  diacetic  acid  had  been  present.  The  patient  consulted  Prof. 
Holsti,  who  affirmed  the  existence  of  diabetes  mellitus,  prescribed  a  strict  diet, 
and  after  some  time  sent  the  patient  to  me  in  Carlsbad.  The  general  state  of 
health  was  then  much  improved,  and  there  were  no  diabetic  symptoms.  A  gen- 
erous amount  of  carbohydrates  was  allowed  and,  no  glycosuria  appearing, 
the  amount  was  slowly  increased  until  it  reached  at  least  300  grams  a  day. 
The  urine  remained  free  from  glucose,  nor  could  that  substance  be  found  after 
administration  of  200  grams  of  cane-sugar.  For  some  time  after  the  patient's 
arrival  at  home  he  continued  to  be  free  from  glycosuria  upon  ordinary  diet, 
but  I  know  nothing  of  his  subsequent  fate. 

In  this,  as  in  some  other  cases,  I  have  no  doubt  the  glycosuria  was  due  to 
the  influenza. 

Blot,  in  1850,  found  in  the  urine  of  pregnant  women  a  variety  of 
sugar  that  Hofmeister  afterward  proved  to  be  lactose.  This  puer- 
peral lactosima  begins  during  the  last  months  of  pregnancy  and 
persists  throughout  the  whole  period  of  lactation,  during  the  begin- 
ning of  which  it  seems  to  be  most  pronounced,  so  that  it  may  reach 
two  per  cent.  Abeles  found  lactose  in  every  one  of  30  cases  ;  Ney 
observed  it  exceptionally  before  parturition,  but  in  80  per  cent,  of 
the  cases  he  detected  it  from  two  to  four  days  after  parturition.* 
Lemaire  found  in  the  urine  quite  small  quantities  of  glucose  and 
isomaltose  before  parturition,  and  lactose  only  after  parturition,  but 
in  large  quantities. 

There  is  no  doubt  that  pregnancy  and  childbirth  sometimes  give 
rise  to  true  glycosuria.  Puerperal  glycosuria  is  much  rarer  than 
puerperal  lactosuria.  I  have  seen  one  patient  who,  after  some 
months  following  parturition,  was  sent  to  Carlsbad  with  a  diagnosis 
of  diabetes.  The  urine  contained  small  quantities  of  a  dextrogy- 
rate-reducing substance,  which  readily  underwent  fermentation  and 
disappeared  in  the  presence  of  common    yeast.     I  am  unable  to 

*See,  besides,  the  treatises  of  Sinety,  Kirsten,  Spiegelberg,  Johannowski,  Hofmeister, 
Kaltenbach,  and  others. 


66  DIABETES    MELLITUS    AND    GLYCOSURIA. 

State  how  long  this  glycosuria  lasted,  but  after  two  years  the  urine, 
with  an  ordinary  free  diet,  contained  no  glucose.  Marcus  men- 
tions glycosuria  up  to  0.7  per  cent,  during  pregnancy;  Rossa 
found  glucose  during  the  seventh  month,  and  Lang  found  that 
pregnancy  is  quite  often  attended  with  some  loss  of  the  power  of 
assimilating  carbohydrates. 

Sometimes  parturition  is  followed  by  true  diabetes. 

The  saccharid  often  found  in  the  urine  of  nursing  infants  is  lac- 
tose (Pollak,  Eichhorst),  which  passes  into  the  urine  more  easily  than 
other  kinds  of  sugar. 

CI.  Bernard  found  sugar  in  the  amniotic  liquor  in  animals,  observed  later  also 
by  Moriggia  and  by  Cramer.  The  amniotic  fluid  contains  the  urine  of  the 
fetus,  and  \.\ns  fetal  glycosuria,  like  the  ,  glycosuria  of  hibernating  animals, 
constitutes  one  of  the  best  arguments  of  those  who  see  in  hyperglycemia  and 
glycosuria  the  effect  of  deficient  combustion  in  the  muscles  ;  but  sugar  in  the 
amniotic  liquor  does  not  seem  to  be  at  all  a  constant  phenomenon  in  normal 
women,  and  it  is  sometimes  absent  even  when  diabetes  exists  in  the  mother 
(Williams,  Naunyn),  though,  like  other  liquids  of  the  organism,  it  may  in  other 
cases  of  diabetes  contain  quite  considerable  (up  to  0.7  per  cent.)  quantities  of 
glucose  (Husband).  Fetal  glycosuria  and  the  glycosuria  of  hibernates  deserve 
further  investigation. 

Obesity  and  Glycosuria. — About  one-third  of  all  diabetic  patients 
are  corpulent ;  and  very  fat  persons,  according  to  several  observers, 
present  more  frequently  than  others  pathologic  traces  of  sugar  in 
their  urine.  I  have,  in  several  instances,  found  that  persons  who 
in  early  middle  age  suddenly  grew  corpulent  at  the  same  time  be- 
gan to  exhibit  distinct  traces  of  sugar  for  a  short  while  after 
meals,  the  urine  having  previously,  under  similar  circumstances  and 
with  the  same  tests,  proved  to  be  normal.  Almost  all  fat  people 
with  glycosuria  present  also  neurasthenic  symptoms.  Some  of 
these  patients  eventually  develop  true  diabetes,  but  generally 
remain  in  the  mild  stage.  Still,  obesity  is  no  safeguard  against 
severe  diabetes  even  exclusive  of  pancreatic  cases  ;  the  severe  dys- 
trophy, however,  within  a  short  time  puts  an  end  to  the  obesity, 
Kisch  beheves  that  in  about  fifty  per  cent,  of  cases  of  hereditary, 
and  in  about  fifteen  per  cent,  of  acquired,  obesity  pathologic  excre- 
tion of  sugar  takes  place  sooner  or  later.  The  first  of  these 
figures  appears  to  me  somewhat  too  high. 


GLYCOSURIAS.  6/ 

Gout  and  Glycosuria. — Gout  is  more  often  than  any  other  disease 
associated  with  glycosuria  or  diabetes.  Any  physician  with  many 
gouty  patients  under  his  care  will,  if  he  adopt  the  practice  of  testing 
at  least  once  the  after-dinner  urine  of  every  patient  for  sugar, 
find  that  a  large  percentage  of  gouty  individuals  excrete  for  some 
time  every  day  distinctly  pathologic  quantities  of  glucose.  This 
glycosuria  may  set  in  before  the  appearance  of  gouty  symptoms, 
which  when  mild  are  often  for  years  overlooked  both  by  patient 
and  physician  ;  in  other  cases  the  urine  remains  normal  for  some 
time  after  the  appearance  of  distinct  gouty  symptoms.  In  all  such 
cases  neurasthenic  symptoms  seem  to  be  present.  Whether  gout 
or  glycosuria  has  been  first  to  make  its  appearance,  no  fact  is  of 
better  prognostic  import  in  a  case  of  glycosuria  than  its  association 
with  gout.  In  almost  all  of  the  many  cases  of  this  kind  that  I  have 
seen  the  glycosuric  dystrophy  has  shown  a  strong  tendency  to 
remain  stationary,  and  often,  for  the  important  purpose  of  encour- 
agement, I  tell  such  patients  that  they  will  never  die  until  somebody 
clubs  them,  which  rarely  fails  to  make  their  faces  brighten  with  the 
most  intense  satisfaction. 

Diabetes  Insipidus  and  Glycosuria. — Over  and  above  polydipsia  and  poly- 
uria as  effects  of  hyperglycemia,  we  may  explain  a  connection  between  dia- 
betes mellitus  and  diabetes  insipidus  by  the  close  proximity  of  the  centers  for 
glycosuria  and  polyuria  on  the  floor  of  the  fourth  ventricle.  The  existence  of  a 
separate  center  for  polyuria  (and  polydipsia) — i.  e.,  diabetes  insipidus — also  ex- 
plains why  neither  the  intensity  nor  the  degree  of  the  glycosuria  has  any  fixed  re- 
lation to  the  degree  of  the  polyuria.  One  patient  may  pass  in  the  twenty-four  hours 
1.5  liters  of  urine  containing  forty  grams  of  glucose,  while  another  may  with  the 
same  amount  of  carbohydrates  and  other  food  pass  in  the  same  time  three  liters 
of  urine  with  twenty  grams  of  glucose.  Many  think,  with  Klemperer,  that  poly- 
uria/^r  se,  by  its  influence  on  the  kidneys,  favors  the  elimination  of  glucose 
with  the  urine,  as  it  favors  the  elimination  of  inosite.  Sometimes,  though 
rarely,  one  therefore  finds  small  quantities  of  sugar,  which  are  too  insignificant 
to  constitute  diabetes  mellitus  in  a  case  of  distinct  diabetes  insipidus  (Mann- 
kopff.  Senator). 

Starvation  and  Glycosuria. — Claude  Bernard  observed  that  dogs, 
after  having  been  subjected  to  starvation,  on  again  receiving  carbo- 
hydrates presented  glycosuria.  Lehman  (1873)  and  Hofmeister 
("  Arch,  f  exp.  Path.,"  1887)  have  made  investigations  in  this  field. 
A  dog,  weighing  two  kilos,  showed,  after  some  days  of  abstinence 


68  DIABETES    MELLITUS    AND    GLYCOSURIA. 

from  food,  distinct  glycosuria  after  the  ingestion  of  as  little  as  ten 
grams  of  starch.  The  sugar  under  such  conditions  appeared  one 
to  two  hours  after  meals,  and  generally  persisted  for  only  a  kw 
hours  in  small  quantities,  although  sometimes  it  reached  nearly  four 
per  cent.  In  their  normal  state  the  animals  generally  were  able  to 
receive  about  five  grams  of  glucose  per  kilo  of  body  weight  with- 
out presenting  glycosuria  ;  after  starvation  the  sugar  appeared  in  the 
urine  after  less  than  two  grams  per  kilo  of  body  weight,  the  rapidity 
of  absorption  from  the  alimentary  canal  being,  in  the  latter  case, 
rather  diminished  than  increased.  It  is  to  be  remembered  that 
starvation  undoubtedly  plays  some  part  in  the  etiology  of  true 
diabetes. 

Fatigue  and  Glycosjiria. — Zimmer  and  others  have  observed  that 
muscular  exercises  up  to  a  certain  point,  in  addition  to  their  cus- 
tomary healthful  influence  on  diabetic  patients,  also  have  a  tendency 
to  diminish  existing  glycosuria  ;  but  too  long  walks,  too  much  phy- 
sical effort  of  any  kind  has  a  contrary  effect ;  and  sometimes  severe 
fatigue  is  followed  by  a  considerable  increase  in  the  amount  of  sugar 
in  the  urine.  The  same  influences  will  sometimes  show  themselves 
in  normal  persons,  so  that  after  muscular  excesses  glycosuria  may 
appear  for  a  short  while  and  quickly  disappear  after  rest. 

Cold  and  Glycosuria. — Bohm  was,  I  think,  the  first  to  mention 
the  slight  glycosuria  that  may  come  on  after  exposure  to  cold  ;  it 
has  since  been  observed  by  Araki  and  others  in  rabbits  and  dogs 
after  application  of  ice  around  the  body.  Exposure  to  severe  cold 
is  not  rarely  mentioned  by  diabetic  patients  themselves  as  a  proba- 
ble cause  of  their  dystrophy. 

Senility  and  Glycosuria. — Small  quantities  of  sugar  often  appear 
in  the  urine  of  old  persons.  This  senile  glycosuria  is  of  no  clinical 
importance,  and  entails  upon  the  physician  no  other  duty  than  to 
withhold  the  fact  from  the  "patient,"  who  might  be  unnecessarily 
alarmed  by  such  an  information. 

Cachexia  or  Marasmus  and  Glycosuria. — In  cases  of  carcinoma, 
tuberculosis,  Addison's  disease  (Burghardt),  leukemia  (Rebitzer),  and 
in  other  diseases  that  are  accompanied  by  marked  cachexia  or  maras- 


GLYCOSURIAS.  69 

mus,  slight  traces  of  glucose  are  often  found  in  the  urine  (Zimmer  and 
others).  On  the  other  hand,  it  is  often  observed  that  the  glyco- 
suria perceptibly  diminishes  in  cases  of  diabetes  as  a  cachectic  or 
marantic  state  develops  (Naunyn  and  others). 

The  Kidneys  and  Glycosuria. — It  is  well  known  that  the  same 
amount  of  hyperglycemia  may  cause  in  different  persons  a  widely 
different  degree  of  glycosuria  (see  Seegen's  figures),  and  there  is  a 
wide -spread  opinion  that  the  kidneys  have  an  influence  on  the  latter 
(Lepine  and  others).  This  opinion  seems  corroborated  by  several 
recently  acquired  facts,  which  I  recapitulate  here. 

The  glycosuria  due  to  phloridzin  seems  to  depend  upon  changes 
in  the  kidneys.  We  know  that  after  extirpation  of  the  pancreas  in 
birds,  whose  normal  glycemia  is  about  0.14  or  0.15  per  cent. 
(Kausch),  the  hyperglycemia  reaches  a  higher  figure  than  in  mam- 
mals before  glycosuria  sets  in  ;  or,  in  other  terms,  that  the  kidneys 
of  birds  have  a  greater  power  of  preventing  the  sugar  of  the  blood 
from  passing  over  into  the  urine  (Kausch).  Klemperer  found,  in 
nephritis,  glycosuria  (of  0.35  per  cent.)  with  a  normal  quantity  of 
sugar  in  the  blood.  Other  changes  in  the  kidneys  seem  also  to 
bring  about  a  diminished  power  of  retaining  the  sugar  of  the  blood. 
Frerichs,  Morison,  Habershon,  and  Pavy  (cited  by  Naunyn)  saw 
chyluria  associated  with  glycosuria.  Naunyn  found  sugar  in  con- 
junction with  hemorrhages  from  the  kidneys.  Jacobi  found  that 
diuretics  (theobromin,  sulphocaffeinic  acid,  "  diuretin  ")  cause  gly- 
cosuria, which  seems  easily  brought  about  in  traces  when  polyuria 
exists  from  any  cause  whatever — e.g.,  diabetes  insipidus.  Most  of 
these  facts,  however,  may  be  explained  in  other  ways,  and  "renal 
glycosuria"  at  the  present  moment  represents  scarcely  more  than 
a  hypothesis. 


70  DIABETES    MELLITUS    AND    GLYCOSURIA. 


CHAPTER  IV.— SYMPTOMS  AND  COMPLICATIONS  OF 
MILD  AND  SEVERE  DIABETES. 

Diabetes  mellitus  is,  as  already  mentioned,  not  a  disease  or  a 
clinical  entity,  but  a  syndrome  that  may  arise  from  a  number  of 
quite  different  processes  in  the  organism.  The  glycosuria  is  not 
necessarily  the  first  in  the  series  of  manifestations  that  mark  the 
change  in  the  patient's  state  of  health. 

In  the  great  majority  of  cases  the  precursory  signs  that  are  not 
rarely  observed  are  referable  to  the  nervous  system  and  belong  to 
the  neurasthenic  group.  When  a  patient,  with  a  urine  still  free 
from  sugar  and  with  nothing  more  abnormal  than  perhaps  the 
presence  of  a  rather  large  quantity  of  crystals  of  calcium  oxalate, 
has  for  some  time  complained  of  insomnia,  irritability,  enfeebled 
sexual  power,  neuralgia,  etc.,  glycosuria  may  appear  and  slowly 
progress.  In  other  less  frequent  cases  changes  in  the  vessels,  new- 
growths,  cerebral  softening,  hemorrhages,  parasites,  or  traumatic 
influences  may  cause  cerebral  symptoms  before  glycosuria  makes 
itself  manifest. 

In  still  other  cases,  and  especially  in  persons  that  are  approach- 
ing middle  age,  I  have  several  times  found  that  the  first  appearance 
of  sugar  in  the  urine  was  preceded  by  a  tendency  to  corpulence, 
whereupon  a  simple  glycosuria  or  a  mild  diabetes  has  set  in. 

In  rare  cases  it  is  possible,  before  glycosuria  begins,  to  diagnos- 
ticate disease  of  the  pancreas,  then  generally  of  carcinomatous 
nature. 

Upon  the  whole,  a  rule  prevails — though  one  with  many  excep- 
tions— that  a  diabetes  that  afterward  pursues  a  mild  course  quite 
imperceptibly  invades  the  patient,  and  years  may  pass  after  the  first 
appearance  of  sugar  in  the  urine  before  an  accidental  analysis,  a 
slowly  increasing  polydipsia,  a  poor  and  complicated  healing- 
process,  or  some  local  complication  direct  the  patient's  or  the  phy- 
sician's suspicions  on  the  right  track.  Many  physicians  omit  the 
important  investigation  of  the  urine,  and  it  often  happens  that  the 
specialist — e.  g.,  the  ophthalmologist  or  the  dermatologist — fore- 
stalls the  family  physician  in  discovering  the  existence  of  diabetes. 


SYMPTOMS   AND  COMPLICATIONS   OF   DIABETES.  /I 

In  other  cases,  especially  in  such  as  prove  to  be  of  a  severe  kind, 
diabetes  sets  in  suddenly  with  marked  glycosuria  and  specific 
diabetic  symptoms,  without  any  prodromal  manifestations. 

Mild,  slowly  developing  diabetes  is  much  more  common  than 
severe  diabetes. 

When  the  secondary  dystrophy,  the  general  disturbance  of  nutri- 
tion, has  developed  in  consequence  of  the  primary  lesion  of  the 
nervous  system,  or  the  pancreas,  etc.,  the  effects  may  be  induced 
in  any  organ  as  a  result  of  either  the  deficiency  on  the  part  of  the 
organism  to  fully  utilize  its  carbohydrates  and  its  consequent  inani- 
tion, or  of  the  action  of  certain  toxins,  or  from  defective  central  or 
peripheral  nervous  influences. 

Among  the  toxins  in  the  blood  we  include  the  superfluous  amount 
of  sugar  contained  therein.  In  mild  cases  this  probably  is  the  only 
toxin,  and  one  whose  deleterious  influence  has  been  enormously 
overrated.  A  glycemia  of  0.15  per  cent,  may  still  be  considered 
not  in  excess  of  the  normal ;  above  0.4  per  cent,  is  found  only  in  a 
small  minority  of  cases  of  diabetes  (Seegen,  Naunyn,  and  others). 
Persons  suffering  from  true  diabetes,  who  can  not  be  persuaded  to 
adhere  strictly  to  a  proper  diet  and  who  constantly  present  glyco- 
suria (and  hyperglycemia)  may  live  in  fairly  good  health  for  more 
than  twenty  years.  This  single  id^cX. proves  that  hyperglycemia /^r  5^ 
can  not  possibly  be  a  very  powerful  nocens.  Its  worst  effect  is  prob- 
ably the  retaining  firmer  than  is  the  normal  the  water  in  the  blood- 
vessels, and  thus,  to  a  certain  extent,  desiccating  the  tissues.  This 
causes  some  disturbance  in  the  nutritive  state  and  the  functional 
power  of  the  organs  ;  it  may,  e.  g.,  bring  about  cataract  and  con- 
tribute to  the  development  of  gangrene,  suppuration,  and  other  dis- 
integrating processes,  or  of  neuritis  and  other  "parenchymatous" 
changes.  The  hyperglycemia  may  also  be  in  part  responsible  for 
the  diabetic  endarteritis  and  the  arteriosclerosis.  The  hyperglyce- 
mia, however,  which  in  most  cases  is  quite  moderate,  generally 
takes  a  very  long  time  to  bring  about  these  changes. 

A  much  more  deleterious  effect  is  attributable  to  the  acid  toxins, 
the  free  fatty  acids,  the  diacetic  acid,  and  the  /5-oxybutyric  acid. 
When  the  physician  sees  for  the  first  time  a  diabetic  patient,  the 
quickest  and  best  way  of  determining  approximately  the  stage  of 
the  diabetic   dystrophy  is  to   make    use  of  Gerhardt's  test,  which 


72  DIABETES    MELLITUS    AND    GLYCOSURIA. 

consists  in  pouring  a  few  drops  of  ferric  chlorid  in  a  tube  nearly 
filled  with  the  patient's  urine.  The  appearance  of  a  beautiful  wine- 
purple  color  denotes  directly  the  presence  in  the  urine  of  diacetic 
acid,  and  indirectly  often  the  presence  of  that  most  ominous  sub- 
stance, /5-oxybutyric  acid  (see  below).  It  may  then  be  concluded 
that  the  patient  is  in  the  severe  stage  of  diabetes,  that  he  has  at 
the  utmost  only  a  few  years  of  life  left,  which  will  pass  in  a  struggle 
with  the  autophagy  and  the  acid  diathesis  ("acidosis  "),  with  all  its 
manifold  dangers,  and  that  death  will  probably  be  caused  by  the 
blood-toxins. 

What  role  each  of  the  different  pathologic  factors — the  toxins 
and  the  deficient  nervous  influences,  etc. — play  in  the  production 
of  anatomic  lesions  is  only  imperfectly  known.  A  good  deal  of 
mystery  surrounds  especially  the  purely  nervous  "trophic"  influ- 
ence and  its  anomalies  in  diabetes  as  in  other  dystrophies. 

In  this  chapter  will  be  considered  dystrophic  general  changes 
and  those  that  occur  in  each  of  the  different  organs.  However 
wide  a  clinical  difference  may  exist  between  a  diabetic  patient  in 
the  mild  and  one  in  the  severe  stage,  there  is  no  distinct  scientific 
demarcation  separating  these  two  stages,  and  it  is  injudicious  to 
contribute  to  the  idea  prevailing  in  some  quarters  of  two  entirely 
different  "forms"  of  diabetes.  I  give,  therefore,  no  separate 
description  of  mild  and  severe  diabetes,  but  only  point  out  the  toxic 
and  cachectic  nature,  and  the  autophagy  of  the  latter,  and  describe 
its  usual  final  scene — diabetic  coma. 

In  connection  with  the  clinical  symptoms,  we  must  consider  the 
pathologic  anatomic  lesions  of  diabetes.  These  are  often  but  Httle 
marked,  both  macroscopically  and  microscopically.  After  the 
existence  of  mild  diabetes,  which  is  not  pei'  sc  fatal,  changes  of  a 
purely  diabetic  character  are  generally  overshadowed  at  the  autopsy 
by  alterations  due  to  the  intercurrent  or  complicating  disease. 
After  diabetes  in  the  severe  stage  or  of  long  standing,  the  autopsy 
is  certainly  very  likely  to  reveal  characteristic  changes.  These, 
however,  even  when  found  in  those  organs  that  play  a  role  in  the 
pathogenesis  of  diabetes, — the  nervous  system,  the  pancreas,  and 
the  liver, — are  far  more  frequently  an  effect  than  a  cause  of  the 
diabetes,  and  represent  retrogressive  and  degenerative  processes 
due  to  the  marasmus   and  the  cachexia.      The  alterations  in  the 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  73 

kidneys,  the  most  frequent  of  all,  have  no   connection    with  the 

origin   of  the  dystrophy,  but  are  the   results   of  its  effects  on  the 
renal  functions. 


SPECIFIC   DIABETIC   AND   DYSTROPHIC   SYMPTOMS. 

The  sugar  that  appears  m  the  urine  in  cases  of  simple  glycosuria 
is  present  in  determinable  quantities  only  for  some  time  after  meals, 
while  in  cases  of  true  diabetes,  however  mild,  it  is  present  under 
continued  ordinary  diet  throughout  the  whole  or,  at  least,  the 
greater  part  of  the  twenty-four  hours,  being  absent  only  when  the 
patient's  stomach  is  empty  just  before  meals,  and  especially  in  the 
morning  before  breakfast.  With  restriction  of  the  carbohydrates 
to  a  quantity  below  the  patient's  power  of  assimilation,  the  sugar 
in  the  mild  stage  of  the  dystrophy  disappears  from  the  urine.  In 
the  severe  stage,  when  glycosuria  is  derived  at  least  partly  from 
proteids,  the  urine  constantly  contains  glucose — except,  perhaps, 
just  before  death,  when  the  entire  metabolism  fails. 

After  carbohydrates  have  been  taken  glycosuria  begins  in  about 
half  an  hour,  and  so  quickly  reaches  its  maximum  that  the  greater 
part  of  the  sugar  in  the  urine  may  have  been  excreted  during  the 
first  hour.  The  whole  excretion  generally  does  not  last  more  than 
five  or  six  hours,  and  often  a  shorter  time.  In  rare  cases  one  some- 
times finds  a  distinct  postponement  of  the  whole  excretion. 

The  glycosuria  following  proteids  in  the  severe  stage  of  the  dys- 
trophy is  attended  with  the  excretion  of  less  sugar,  and  reaches 
its  maximum  later  than  after  ingestion  of  carbohydrates  ;  or,  in 
other  words,  the  glycosuric  curve  due  to  proteids  shows  a  lower 
wave. 

The  intensity  of  the  glycosuria — i.  e.,  the  amount  of  glucose  ex- 
creted in  twenty-four  hours — varies  greatly,  and  depends  on  the 
power  of  assimilation  and  on  the  quality  and  quantity  of  the  food 
ingested.  In  cases  of  true  diabetes,  however,  after  prolonged  free 
diet  it  generally  reaches  a  considerable  degree  and  always  some 
number  of  grams.  Anything  below  one,  or  even  two,  grams  under 
such  circumstances  is  properly  considered  simple  glycosuria. 
Sometimes  the  glycosuria  reaches  quite  extraordinary  figures,  and 
it  may  reach  one  kilo,  in  twenty-four  hours.  Dickinson  found  in 
6 


74  DIABETES    MELLITUS    AND    GLYCOSURIA. 

one  case  1500  grams,  and  some  French  observers  have  noted  still 
higher  figures. 

The  mtensity  of  the  glycosuria — /.  e. ,  the  percentage  of  glucose — 
varies  exceedingly  during  the  twenty-four  hours.  The  minimum  is 
always  found  in  the  morning  before  the  patient's  first  meal,  and  a 
large  number  of  diabetics  present  at  this  time  of  day  no  glycosuria 
that  is  discoverable  with  our  ordinary  tests.  The  maximum  is 
generally  reached  between  one  and  two  hours  after  meals,  and  there 
are  usually  three  distinct  waves  during  the  twenty-four  hours,  their 
height  depending  on  the  nature  of  the  food.  With  a  strict  diet  no 
reaction  may  be  observed  in  mild  cases  or  only  a  slight  one. 
In  advanced  cases,  with  a  liberal  supply  of  carbohydrates  we  some- 
times find  ten  per  cent,  of  sugar.  Naunyn  noted  eleven  per 
cent.  Higgins  and  Ogden  speak  of  twenty  per  cent.  (?)  Urine 
containing  more  than  six  per  cent,  of  sugar  is  rare.  In  the  course 
of  an  enormous  number  of  analyses  I  have  found  some  few  show 
more  than  nine  per  cent.,  but  only  one  reaching  ten  per  cent. 
The  percentage  of  glucose,  depending  under  all  circumstances 
largely  on  the  quantity  and  quality  of  the  food,  forms  in  itself  only 
a  vague  expression  of  the  intensity  of  the  diabetic  dystrophy.* 

A  patient  living  exclusively  on  meat  and  fat  (water  and  salts), 
with  0.3  per  cent,  of  glucose  in  his  urine,  is  much  worse  off  than 
another  living  on  an  abundant  ordinary  mixed  diet,  with  three  per 
cent,  of  glucose  in  his  urine.  The  same  patient  who,  one  or  two 
hours  after  dinner,  exhibits  three  per  cent,  of  sugar  in  his  urine, 
may  early  the  next  morning  exhibit  only  0.05  per  cent.  When  I 
hear  of  any  one  whose  urine  contains  from  three  to  five  or  seven 
per  cent,  of  glucose,  I  conclude  that  he  is  diabetic — nothing  more  ; 
but  if  I  hear  of  some  one  whose  urine  contains  0.5  per  cent,  of  glu- 
cose, I  gain  scarcely  any  information  at  all  about  his  case — it  may  be 
one  of  simple  glycosuria,  or  of  mild  or  severe  diabetes.  When  I 
hear   of  any  one  whose  urine   contains   0.5   per  cent,  of  glucose. 


*  Bouchard  unconditionally  and  sans  phrase  proposes  to  designate  as  severe  every  case 
of  diabetes  with  an  excretion  of  over  fifty  grains  of  glucose  in  the  twenty-four  hours  ;  and 
as  mild,  every  case  with  less  than  this  amount.  This  is  for  me  a  most  striking  illustration 
of  the  possibility  of  complete  absences  intellectuelles,  even  in  men  of  genius.  Many  a 
diabetic  patient  may,  according  to  this  most  extraordinary  classification,  repeatedly  be  a 
severe  case  on  Mondays  and  a  mild  one  on  Tuesdays,  and  vice  versa. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  75 

with  Strict  diet,  this  at  once  tells  me  that  he  is  in  the  severe  stage. 
It  is  useless  to  give  figures  of  the  glycosuria  without  some  infor- 
mation as  to  the  diet. 

With  an  exclusive  diet  of  meat  and  fat,  glycosuria,  which  dis- 
appears entirely  in  the  mild  diabetic  stage,  rarely  reaches  above 
two  or  three  per  cent,  in  the  severe  stage. 

In  severe  cases  the  patient  often  passes  a  clear,  pale,  greenish- 
yellow  urine  with  a  specific  gravity  that  often  is  nearer  1.040  than 
1.030,  and  that  sometimes  may  reach  far  above  the  first  figure. 
Several  observers  mention  1.070;  Proust  and  Bouchard,  1.074. 
Diabetic  urine,  however,  especially  in  mild  cases,  varies  enor- 
mously in  appearance,  specific  gravity,  and  other  qualities.  A  dia- 
betic in  the  mild  stage,  when  he  has  not  received  carbohydrates 
beyond  his  limit  of  assimilation,  passes  urine  that,  besides  being 
free  from  glucose,  is  otherwise  scarcely  different  from  that  which 
a  healthy  person  passes  under  the  same  dietetic  conditions.  We 
quite  frequently  find,  even  in  severe  cases,  a  urine  of  perfectly  nor- 
mal, sometimes  even  a  somewhat  high,  yellow  color,  and  in  mild 
cases  not  rarely  a  strong  sediment  of  uric  acid.  Under  the  micro- 
scope the  conditions  often  are  normal,  although  sometimes  there 
may  be  a  rather  large  amount  of  the  small  crystals  of  calcium  oxal- 
ate and  sometimes  also  occasionally  hyaline  and  more  rarely 
granular  casts.  The  nitric-acid  test  not  uncommonly  discloses 
the  presence  of  albumin,  and  the  colored  zone  above  the  acid 
is  frequently  pronounced.  By  reason  of  the  abundance  of  animal 
food  the  urea  and  other  derivatives  of  proteids  are  generally  pres- 
ent in  rather  large  quantities,  and  the  specific  gravity,  therefore,  is 
often  high,  even  when  no  sugar  is  present.  In  many  cases  in  the 
mild  stage,  however,  the  specific  gravity  is  below  1.030,  and  not 
only  within  normal  but  within  very  common  limits.*  One  may 
find  urines  of  a  specific  gravity  of  1.020  that  contain  quite  a  con- 
siderable amount  (above  one  per  cent.)  of  glucose.  Sometimes 
one  may  even  find  distinctly  pathologic,  though  small,  quantities 
of  glucose  in  urine  of  an  exceptionally  low  specific  gravity.     Some 

*  A  normal  middle-aged  man,  who  eats  much  meat,  often  passes  urine  of  a  specific 
gravity  nearer  1.030  than  1.020.  One  may  sometimes,  apart  from  diabetes,  even  find 
the  urine  of  comparatively  normal  persons  with  quite  a  high  specific  gravity.  Only  re- 
cently I  encountered  a  specific  gravity  of  1.034  in  such  a  case. 


■j6  DIABETES    MELLITUS    AND    GLYCOSURIA. 

time  ago  I  saw  a  urine  of  1.005  specific  gravity  undergo  a  beauti- 
ful reduction  with  Nylander's  and  Fehling's  solutions  before,  but 
not  after,  fermentation.  It  came  from  a  gouty  patient  with  simple 
glycosuria,  who  had  been  on  a  spree  and  had  drunk  two  quarts  of 
beer.  True,  though  mild,  diabetes  may  give  rise  to  exactly  such  a 
urine  either  after  prolonged  abstinence  from  carbohydrates  or  dur- 
ing one  of  those  periods,  sometimes  observed  in  mild  cases,  when 
the  power  of  assimilation  becomes  very  high  or,  finally,  when  some 
care  in  diet  has  been  observed,  but  much  water  has  been  drunk. 

It  is  interesting  to  note  the  differences  in  view  as  to  the  fre- 
quency of  albuminuria  in  association  with  diabetes.  Schmitz  noted 
albuminuria  in  68.6  per  cent.  (!?),*  Bouchard  in  43  per  cent., 
V.  Dusch  in  25  per  cent.,  Garrod  in  10  per  cent,  of  their  cases  of 
diabetes.  Grube  (1878)  states  that  he  found  albumin  in  the  urine 
in  191  of  473  cases  of  diabetes,  or  in  40  per  cent.  In  the  severe 
stage  of  the  disease  albuminuria  is  much  more  frequent  than  in  the 
mild  stage.  Including  all  cases  of  true  diabetes  in  private  practice, 
it  will  be  found  that  Grube's  figures,  which  certainly  are  rather  too 
high  than  too  low,  best  represent  the  truth,  while  in  hospitals, 
where  chiefly  severe  cases  are  found,  the  figures  will  be  consider- 
ably higher  (see  below). 

In  some  cases  the  solution  of  ferric  chlorid  shows  the  presence 
oi  diacetic  acid  (Gerhardt's  most  important  reaction),  which,  except 
with  inanition,  is  absent  in  mild  cases. 

For  the  other  changes  in  diabetic  urine  I  refer  the  reader  to  the 
chapter  on  Metabolism. 

hicrcased  thirst,  polydipsia,  and  polyuria  are,  as  is  well  known, 
frequent  symptoms  of  diabetes,  and  hold  a  causal  relation  with 
each  other,  which  is  still  far  from  perfectly  understood.  Thirst 
and  polydipsia  are  certainly  causes  of  polyuria,  and  any  one, 
whether  diabetic  or  not,  who  drinks  much,  will  pass  a  large  quan- 
tity of  urine.  The  increased  thirst  of  diabetes  must  arise  from  the 
increased  amount  of  sugar  in  the  blood,  which  keeps  the  water  in 
the  vessels  firmer  than  normal,  and  dries  the  tissues,  which  still  are 
thirsting  when  a  normal  quantity  of  water  is  ingested,  just  as  they 


*  These  figures  can  scarcely  be  explained  in  any  otherJway  than  by  the  zone  of  urates 
(with  Heller's  test)  having  been  mistaken  for  one  of  albumin. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  // 

may  hunger  from  the  loss  of  glucose  and  from  the  protoplasmic 
disintegration  (see  below)  with  a  normal  supply  of  food.  Hyper- 
glycemia in  itself  acts  on  the  kidneys  as  a  diuretic.  When  enor- 
mous doses  of  saccharids  are  given,  the  urine  always  suddenly 
increases.*  To  some  extent  an  increased  want  of  water  arises 
within  the  organism  merely  in  consequence  of  the  carbohydrates 
passing  off  as  glucose  instead  of  being  oxidized  into  water  and  car- 
bonic acid.  If  the  supply  of  carbohydrates  in  the  food  is  restricted 
and  hyperglycemia  and  glycosuria  cease,  polydipsia  and  polyuria 
often  also  cease. 

Polyuria  may,  however,  arise  also  in  consequence  of  direct  vaso- 
motor influences,  and  not  be  the  effect  but  the  cause  of  increased 
thirst  and  polydipsia.  Thus,  lesion  of  the  "  lobus  hydruricus  "  in 
the  vermis,  near  the  seat  for  Bernard's  puncture,  causes  diabetes 
insipidus,  as  does  also  lesion  of  Kahler's  centers.  Further,  the  in- 
creased excretion  of  urine  is  observed  in  progressive  paralysis. 
These  facts  suffice  to  explain,  easily,  cases  of  diabetes  mellitus  with 
slight  glycosuria  and  marked  polyuria,  and  cases  of  diabetes  insipi- 
dus with  slight  traces  of  sugar,  and  the  circumstance  that  the  poly- 
uria sometimes  remains  after  the  disappearance  of  the  glycosuria  in 
the  rare  cases  of  incomplete  recovery  from  diabetes  mellitus. 

Sometimes  cirrhosis  of  the  kidneys  contributes  to  the  polyuria 
and  polydipsia  of  diabetes  mellitus  ;  in  these  cases,  often  of  a  gouty 
nature,  the  sugar  in  the  urine,  from  some  unknown  cause,  usually 
decreases  as  the  cirrhosis  advances. 

Pick  mentions  that  ingested  water  passes  through  the  kidneys  in 
a  shorter  time  in  diabetics  than  in  normal  persons. 

The  quantity  of  urine  is  generally  increased  only  moderately — to 
two  or  three  liters.  More  than  five  hters  is  rare,  except  in  hospital 
practice  with  almost  exclusively  severe  cases.  Sometimes  enormous 
quantities  are  observed.  Dobson  noted  14,  Cantani  also  14,  Fiir- 
bringer  17  liters  ;  Schindler  mentions  16  liters  in  a  child,  etc. 
Such  quantities  always  belong  to  the  most  severe  cases. 

Increased  thirst,  polydipsia  and  polyuria  do  not,  however,  consti- 
tute such  constant  symptoms  as  many  members  of  the  medical  pro- 


*  The  frequency  of  the  pulse  decreases,  but  the  systolic  and  diastolic  excursions  of 
the  heart  become  greater  (Vespa). 


yS  DIABETES    MELLITUS    AND    GLYCOSURIA. 

fession  seem  to  think.  In  the  severe  stage,  especially  regardless 
of  diet,  this  group  of  symptoms  is  certainly,  as  a  general  thing, 
quite  pronounced.  In  the  mild  stage,  even  apart  from  diet,  the 
quantity  of  urine  often  keeps  within  the  normal,  and  the  condition 
corresponds  with  what  already  Peter  Frank  has  called  diabetes  decip- 
iens.  Even  a  moderate  restriction  of  carbohydrates  \\'\\\  in  this 
stage  keep  the  quantity  of  urine  within  normal  limits  in  about 
fifty  per  cent,  of  the  cases.  Sometimes  diabetic  patients  may  pass 
even  an  exceptionally  small  quantity  of  urine  in  the  tw^enty-four 
hours.  I  have  observed  cases  in  which  only  900,  800,  and  700 
cu.  cm.  were  passed. 

I  have  records  of  65  diabetic  patients,  whose  urine  has  been  measured 
for  the  twenty-four  hours  during  a  somewhat  considerable  time,  and  find 
that  of  27  in  the  severe  stage,  22  have  generally  passed  more,  and  5  less, 
than  1600  cu.  cm. ;  and  that  of  38  mild  cases,  half  the  number  have  passed 
less,  the  other  half  more,  than  this  quantity.  All  of  these  patients  were  of  high 
stature,  and  include  Scandinavians,  Britons,  Germans,  and  Americans.  On 
the  other  hand,  it  may  be  conceded  that  almost  all  the  possible  errors  in  meas- 
uring have  contributed  to  malce  the  figures  too  low ;  and  that  in  many  cases 
the  diet  has  corrected  a  preexisting  polyuria. 

As  the  quantity  of  glucose,  so  also  the  quantity  of  urine,  is  gen- 
erally larger  during  the  day  than  during  the  night ;  but  the  rule 
has  many  exceptions,  both  glycosuria  and  polyuria  depending  on 
the  character  of  the  food.  Thus,  when  the  largest  meal,  dinner,  is 
taken  late  in  the  evening,  the  urine  and  the  glucose  often  reach 
higher  figures  during  the  night  than  during  the  day.  Increased 
intensity  of  glycosuria  is,  as  a  rule,  accompanied  by  increased 
intensity  of  polyuria. 

Pollakiuria,  or  abnormally  frequent  passing  of  urine,  is  a  com- 
mon symptom,  but  stands  in  no  distinct  relation  with  the  intensity 
of  either  the  glycosuria  or  the  polyuria.  Sometimes  there  is  dis- 
tinct pollakiuria  without  any  polyuria,  and  the  patient  passes  urine 
a  dozen  times  a  day,  although  the  whole  quantity  may  not  exceed 
the  normal.  In  other  cases,  sometimes  even  in  severe  cases,  there 
is  no  pollakiuria,  but  a  decided  polyuria.  One  of  my  patients,  who 
died  in  coma,  used,  with  great  regularity,  to  pass  urine  only  four 
times  in  twenty -four  hours,  but  each  time  the  quantity  approached 
a  liter. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  79 

Among  symptoms  of  diabetes  may  be  mentioned  the  diminution 
in  the  secretions  and  excretions  other  than  the  urine,  although  exact 
investigations  are  still  scanty.  Of  the  saliva  this  has  been  long  known, 
and  dryness  of  mouth  is  one  of  the  most  common  complaints  of  dia- 
betics. In  mild  cases  one  often  finds  perspiration  normal,  some- 
times abundant,  even  to  hyperidrosis  ;  but  in  advanced  cases  a 
decrease  in  the  secretion  of  the  glands  of  the  skin  is  generally  mani- 
fest, with  asteatosis  and  anhidrosis  and  an  extreme  dryness  of  the 
skin.  Gall-stones  are  more  common  among  diabetics  than  among 
other  persons,  and  this  I  consider  probably  the  result  of  a  decrease 
in  the  secretion  of  bile,  and  chiefly  the  water  thereof.*  Young 
diabetic  men  with  undiminished  sexual  vigor  sometimes  mention 
symptoms  indicative  of  a  diminished  secretion  of  spermatic  fluid. 
The  decrease  in  the  secretions  is  doubtless  due  in  part  to  the  des- 
iccating influence  of  the  hyperglycemia  on  the  glands  as  well  as  on 
other  tissues.  In  severe  cases,  however,  with  marasmus,  atrophic 
and  degenerative  changes  of  the  different  glandular  elements  surely 
contribute  largely  to  this  result. 

Excessive  hunger — bulimia — is  a  common  symptom  in  the  severe 
stage  of  diabetes.  In  the  mild  stage  it  appears  only  in  compara- 
tively advanced  cases  with  a  low  power  of  assimilation  and  a  diet 
too  rich  in  carbohydrates,  when  a  considerable  part  of  the  food 
passes  off  in  the  urine  as  glucose. 

In  the  severe  stage  the  increased  hunger  is  so  far  a  favorable 
manifestation,  as  it  alone  enables  the  patient  to  make  good  the  loss 
of  glucose  and  to  mitigate  the  consequences  of  the  protoplasmic 
disintegration  taking  place  in  the  tissues.  The  ingested  proteids 
under  such  circumstances  sometimes  develop  enormous  values,  and 
I  have  more  than  once  seen  patients  who  for  a  short  time,  in  addi- 
tion to  large  quantities  of  butter  and  moderate  portions  of  carbohy- 
drates, were  able  to  take  considerably  over  one  kilogram  of  cooked 
beef  a  day.  In  far  advanced  cases  the  patient  may  even,  with  such 
food  and  with  an  excellent  digestion,  present  a  clinical  picture  that 

*  Bouchard  states  that  ten  per  cent,  of  all  diabetics  suffer  from  gall-stones.  Even  if 
this  figure  should  be  somewhat  exaggerated,  there  can  scarcely  be  any  doubt  about  the 
increased  frequency  of  gall-stones  in  diabetics.  All  other  explanations  than  the  one  given 
here  of  the  connection  betvi^een  diabetes  and  gall-stones  (by  I.  Kraus)  seem  to  me  to 
lack  any  rational  basis. 


80  DIABETES    MELLITUS    AND    GLYCOSURIA. 

strongly  resembles  that  presented  by  starvation.  In  both  instances 
there  are  observed  constant  loss  of  weight,  utter  prostration,  low- 
bodily  temperature,  decrease  in  the  secretions,  and  the  presence 
in  the  urine  of  acetone,  diacetic  acid,  /3-oxybutyric  acid,  and  increased 
ammonia.  The  final  scene  increases  the  similarity,  for  death  from 
starvation  is  partly  due  to  the  acid  toxins  in  the  blood  already  men- 
tioned, and  is,  so  far,  death  from  poisoning,  with  a  clinical  picture 
that  strongly  resembles  diabetic  coma. 

Instead  of  bulimia,  anorexia  is  sometimes  observed  in  cases  of 
diabetes  of  all  stages.  This  is  a  most  ominous  manifestation  in  the 
severe  stage  of  the  dystrophy,  and  I  shall  return  later  on  to  this 
subject. 

Loss  of  weight  belongs  essentially  to  the  severe  stage,  but  it  may 
occur  under  varying  circumstances,  and  it  can  as  little  as  the  gly- 
cosuria or  other  manifestations  of  derangement  of  metabolism  be 
rightly  considered  clinically  without  reference  to  the  food. 

During  periods  of  great  restriction  or  even  exclusion  of  carbohy- 
drates every  one,  whether  diabetic  or  not,  is  likely  to  lose  in  weight, 
because  it  is  generally  difficult  without  carbohydrates  to  supply  the 
organism  with  the  necessary  amount  of  heat-units.  Loss  of  flesh 
of  this  purely  "alimentary"  kind  is  of  no  clinical  importance  at  all, 
and  does  not  constitute  a  contraindication  against  a  rational,  periodic, 
rigid  restriction  of  carbohydrates.  The  patient  will  afterward,  under 
a  somewhat  freer  diet,  easily  recover  his  loss. 

Then  we  sometimes  find  loss  of  weight,  even  in  the  mild  stage, 
before  the  patient  has  been  put  upon  a  restricted  diet,  and  before  his 
dystrophy  has  been  discovered.  Such  a  loss  of  flesh  is  of  greater 
importance,  and  generally  takes  place  when  the  power  of  assimi- 
lating carbohydrates  is  considerably  impaired  and  they  constitute  a 
large  part  of  the  food.  Still,  it  is  usually  no  very  difficult  task  in 
the  milder  stage  to  check  the  loss  of  weight,  or  even  to  make  it 
good,  by  increasing  the  proteids  and  fat  of  the  food  (and  duly 
reducing  the  carbohydrates). 

Finally,  the  most  marked  and  the  most  important  loss  of  weight 
takes  place  in  the  severe  stage.  When  the  patient's  power  of 
assimilating  carbohydrates  has  reached  a  very  low  point ;  when  he 
loses  in  the  form  of  glucose  even  a  considerable  part  of  the  ingested 
proteids ;    when  the    toxic    protoplasmic    disintegration    of  tissues 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  61 

entails  a  greater  nitrogenous  expenditure  than  income,  and  a  daily 
deficit  under  any  dietetic  conditions  ;  when  the  tissues  are  still 
insufficiently  supplied,  although  the  digestive  apparatus  has  been 
satiated,  then  appears  the  terrible  diabetic  autophagia.  The  loss  of 
weight  under  these  circumstances  is,  in  spite  of  all  dietetic  measures, 
often  exceedingly  rapid,  and  affects  not  only  the  fat  and  the  carbo- 
hydrates of  the  organism,  but  also  the  proteids,  and  probably  often 
the  bones,  and  a  fatal  issue  may  be  looked  for  in  the  immediate 
future. 

The  great  vtdnerability  and  diminished  recuperative  power  of  the 
diabetic  have  been  long  known.  They  are  due  to  the  hypergly- 
cemia and  the  toxins  in  the  blood  and  to  the  dryness  of  the  tissues, 
probably  also  to  defective  nervous  influences.  The  changes  in  the 
vessels,  especially  the  diabetic  endarteritis  in  the  smaller  vessels, 
must  also  have  a  marked  influence  in  this  direction.  This  weak- 
ness is  found  not  only  in  the  severe  stage,  but  it  is  often  quite 
extreme  in  patients  who,  with  restricted  diet,  are  free  from  glyco- 
suria, but  who  have  suffered  from  diabetes  during  many  years.  In 
such  persons  wounds  remain  open  for  a  long  time,  heal  less  often 
without  suppuration,  and  have  pigmented  cicatrices.  The  impaired 
healing  power  in  cases  of  diabetes  has  restrained  surgeons  from 
many  a  necessary  operation,  and  does  so  sometimes  even  yet, 
although  the  diabetic  patient  has  profited  still  more  than  others  by 
aseptic  and  antiseptic  prophylaxis.  Inflammatory  and  suppurative 
processes,  especially  in  inveterate  cases  of  diabetes,  are  much  to  be 
dreaded,  and  a  carbuncle  is  a  far  more  serious  matter  in  a  diabetic 
than  in  a  nondiabetic  person. 

The  dry  tissues,  the  hyperglycemia,  the  toxins,  the  defective  ner- 
vous influences,  the  arteriosclerosis,  and  the  peculiar  changes  in 
the  small  vessels  of  the  diabetic  render  him  more  susceptible  to 
gangrene  than  others. 

Diabetic  gangrene,"^  which  sometimes  develops  in  the  sequence  of 
traumatism  or  other  accidental  agency,  and  sometimes  appears  spon- 
taneously, is  comparable  to  senile  gangrene  ;  in  fact,  it  is  usually  the 


*  Marechal  de  Calvi  and  Hodgkin  (1864)  were  the  first  to  point  out  a  causal  connec- 
tion between  diabetes  and  gangrene.     Peyrot  (1878),  Giron  (1881),  W.  Hunt  (if 
Heidenhain  (i89l),N.  S.  Davis  (1898),  and  others,  have  since  treated  of  the  subject. 


82  DIABETES    MELLITUS   AND    GLYCOSURIA. 

expression  of  both  diabetes  and  senility.  Of  38  cases  of  diabetic 
gangrene  in  the  city  of  Philadelphia,  the  age  in  i  case  was  between 
thirty  and  forty ;  in  2  cases,  between  forty  and  fifty ;  in  11 
cases,  between  fifty  and  sixty ;  in  1 2  cases,  between  sixty  and 
seventy  ;  in  10  cases,  between  seventy  and  eighty  ;  and  in  2  cases, 
between  eighty  and  ninety  years  (Hunt).  It  is  thus  seen  that  the 
cases  are  rare  before  fifty,  begin  to  be  more  frequent  with  advancing 
years,  and  are  relatively  more  frequent  late  in  life.  Diabetic  gan- 
grene is  almost  always  of  the  moist  variety,  and  is  generally  with- 
out a  sharp  line  of  demarcation.  It  usually  attacks  the  lower  ex- 
tremities, especially  the  feet,  but  it  may  occur  almost  anywhere — 
on  the  body,  in  the  lungs,  on  the  arms,  the  nose,  the  penis,  etc. 
Sometimes  the  gangrene  develops  in  several  places  simultaneously 
in  smaller  or  larger  patches.  Settenbom  has  recently  described  a 
case  presenting  such  patches  with  a  circumference  of  from  10  to  15 
cm.,  distributed  over  the  whole  body  except  the  head.  Kaposi 
mentions  a  case  with  "  gangrena  bullosa  serpiginosa  "  ;  and  Pitres, 
Rosenblath,  Blau,  and  others  have  also  described  cases  with  multi- 
ple gangrene  of  the  skin.  Diabetic  gangrene,  chiefly  a  manifesta- 
tion of  old  age,  does  not  usually  occur  in  the  severe  stage,  which  is 
rare  late  in  life  and  of  comparatively  short  duration,  but  in  cases  in 
which  the  exclusion  of  carbohydrates  leads  to  disappearance  of  the 
glycosuria,  though  many  years  of  diabetes  have  had  time,  in 
combination  with  senility,  to  bring  about  the  changes  already 
mentioned.  I  have  myself  seen  several  cases  in  which  the  power 
of  assimilation  was  comparatively  quite  considerable,  although  the 
dystrophy  had  existed  for  between  fifteen  and  eighteen  years.  In 
one  of  the  cases  there  was  marked  arteriosclerosis  and  atrophy  of 
the  kidneys. 

The  prognosis  of  diabetic  gangrene  is  always  dubious,  but  even 
pulmonary  gangrene  is  not  necessarily  fatal.  One  of  my  patients 
has  successfully  passed  through  this  complication.  In  the  lower 
extremities  gangrene  may  often,  under  rational  treatment,  general 
and  local,  result  in  recovery.  I  have  seen  one  case  in  which  an 
enormous  scar  on  the  calf  of  the  left  leg  reminded  the  patient  dur- 
ing the  last  three  years  of  his  life  that  he  had  undergone  such  a 
process. 

The  variety  of  gangrene  due  to  pressure,  and  usually  designated 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  83 

decubitus  (bed-sore),  is  more  easily  acquired  in  diabetes  than  in 
other  conditions,  and  one  has  to  be  especially  on  his  guard  against 
such  a  complication  in  the  course  of  intercurrent  diseases  or  other 
states  that  are  likely  to  cause  it. 

Among  complications  of  diabetes  with  gangrene,  suppuration, 
and  disintegration  of  tissues,  must  be  mentioned  the  common 
furuncle  and  the  carbuncle,  3Md  the  two  rare  disorders,  '' le  mal 
perforant"  and  "Raynaud's  disease.'' 

The  furuncle  is  exceedingly  common,  and  is  especially  to  be 
found  in  the  mild  stage  in  fat  patients  ;  the  thin,  severely  ill  diabetic 
usually  have  had  no  furuncle.  The  complication  is  generally  not  a 
dangerous  one. 

The  carbuncle,  which  generally  appears  on  the  neck  or  on  the 
back,  belongs  to  advanced  cases,  is,  when  associated  with  diabetes, 
quite  a  formidable  disorder,  and  manifests  a  marked  tendency  to 
spread  and  to  give  rise  to  general  septic  infection.  It  causes  death 
in  a  not  inconsiderable  number  of  cases  of  diabetes.  "  Le  inal per- 
forant"  (Kirmisson,  Gascuel)  is,  as  is  well  known,  generally  a 
symptom  of  tabes  dorsalis  ;  if  it  is  found  in  other  cases  one  must 
suspect  diabetes  mellitus.  It  is  sometimes  found  together  with 
diabetic  gangrene  of  the  ordinary  form.  I  have  seen  it  several 
times,  and  I  suppose  that  it  occurs  in  at  least  two  or  three  percent, 
of  all  cases.  The  small,  sharp-edged,  perfectly  round,  torpid  ulcers 
may  occur  on  one  or  both  sides,  generally  on  the  hands  or  feet,  and 
mostly  over  a  joint.  The  innocent-looking  ulcer  then  advances 
into  the  joint,  and  may  cause  extensive  destruction  of  both  the  soft 
tissues  and  the  bones  and  necessitate  amputation.  It  sometimes 
leads  to  death.  The  cases  of  "  mal  perforant "  that  I  have  seen 
have  presented  typical  symptoms  of  neuritis  in  the  affected  area, 
and  neuritis  has  been  repeatedly  found  postmortem. 

That  most  interesting  of  all  forms  of  gangrene,  Raynaud's  disease, 
is  rare  both  in  association  with  and  independently  of  diabetes  ;  but 
the  considerable  number  of  cases  of  diabetes  thus  complicated  leave 
no  doubt  that  diabetes  is  a  predisposing  cause.  "  Raynaud's  dis- 
ease "  is  a  vasomotor  disorder,  and  neuritis  has  several  times  been 
demonstrated  postmortem.  As  is  well  known,  the  disease  often 
attacks  peripheral  parts  symmetrically,  as  the  feet,  the  hands,  or 
the  ears.      It  begins  with  strong  vasomotor  spasm,  giving  rise  to 


84  DIABETES    MELLITUS    AND    GLYCOSURIA. 

ischemia,  pallor,  coldness,  and  some  loss  of  sensibility  in  the  affected 
region.  I  presume  it  is  this  "local  syncope"  that  under  some  con- 
ditions may  lead  to  scleroderma.  After  some  time,  however, — hours 
or  days  or  weeks, — dilatation  of  the  vessels  usually  follows,  with 
hyperemia,  cyanosis,  and  excruciating  pains, — whether  from  active 
vasodilator  influence  or  from  vasoconstrictor  paralysis,  has  not  yet 
been  agreed  upon.  We  have  then  the  "  local  asphyxia,"  which 
some  consider  identical  with  erythromelalgia  as  described  by  Weir 
Mitchell.     After  this,  gangrene  may  set  in. 

Lymphangitis  and  erysipelatous  and  p]ilegnio7ious  processes  threaten 
the  diabetic  much  more  frequently  than  healthy  persons,  probably 
on  account  of  the  better  conditions  for  vegetation  that  he  presents 
to  microorganisms.  Senator  and  Rovere  have  described  cases  of 
suppurative  polymyositis  with  multiple  abscesses  in  the  muscles.  I 
am  unable  to  understand  in  what  respect  such  a  process  differs 
essentially  from  some  cases  of  pyemia. 

Tlie  cavity  of  the  mouth  often  presents  characteristic  changes, 
which  are  of  serious  import  to  the  patient  and  of  practical  signifi- 
cance to  the  physician,  because  they  stand  in  a  certain  relation  to 
the  duration  and  the  intensity  of  the  glycosuric  dystrophy.  The 
breath  gives  at  once  important  information,  its  strong  odor  of  acetone, 
which  is  much  like  that  of  chloroform,  denoting  the  severe  stage 
of  the  dystrophy.  This  odor  may  diffuse  itself  throughout  the 
patient's  room,  often  suggesting  the  diagnosis  immediately,  and 
sometimes  revealing  to  a  physician  the  state  and  the  impending 
fate  of  some  stranger  passing  on  the  street.  One  may  sometimes 
perceive  a  slight  uncertain  odor  of  acetone  from  the  mouth  of  a 
person  in  the  mild  stage  of  diabetes,  as  one  always  does  from  the 
mouth  of  anybody  in  a  state  of  severe  inanition  and  sometimes 
does  from  the  mouths  of  quite  healthy  children.  If  there  is  no 
odor  of  acetone  from  the  mouth  of  a  diabetic  patient,  he  is  pretty 
certain  to  be  in  the  mild  stage.  Inspection  of  the  mouth  also  very 
often  affords  valuable  information.  The  tongiie  is  often  somewhat 
dry  in  mild  cases  of  diabetes,  but  otherwise  it  is  usually  little 
changed.  In  severe  or  advanced  cases  it  is  dry  and  marked  off 
into  rectangular  areas  by  deep  furrows,  like  the  hide  of  an  alligator  ; 
the  base  is  often  covered  by  a  brown,  sometimes  almost  black,  coat- 
ing,  while   the  apex  is   abnormally  red,   with   hyperemic  papillae. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  85 

Here  and  there  one  sometimes  finds  glossy,  fleshy  looking  patches, 
where  the  mucous  membrane  has  undergone  atrophic  changes. 
The  teeth  also  undergo  changes  after  true  diabetes  has  existed  for 
any  great  length  of  time.  If  I  find  a  complete  and  normal  set  of 
teeth,  I  know  at  once  that  the  glycosuria  (and  hyperglycemia)  is 
either  of  recent  date  or  does  not  amount  to  a  true  diabetes.  In 
diabetics,  even  in  the  mild  stage,  the  teeth  are,  as  a  rule,  cariotis  ;  a 
smaller  or  greater  number  of  them,  besides,  have  fallen  out.  In- 
spection of  the  gums  often  leads  to  discovery  of  the  causes  of  loss 
of  teeth.  A  distinct  gingivitis  is  often  present,  exhibiting  tender, 
swollen,  red  areas.  Here  and  there  a  drop  of  pus  may  be  made  to 
appear  on  pressure  ;  the  bistoury  may  empty  a  little  pocket  of  pus  ; 
and  the  probe  may,  through  a  fistula,  reach  bone.  These  features 
belong  to  the  common  condition  of  alveola}'-  pyorrhea.  Sometimes 
the  patient  presents  the  ordinary  symptoms  arising  from  a  more  or 
less  pronounced  periostitis,  or  a  pericementitis,  as,  I  believe,  the 
dentists  call  the  process  when  it  affects  the  periosteum  surrounding 
the  roots  of  the  teeth.  In  some  cases,  even  independently  of 
senility,  teeth  are  missing  without  any  evidence  of  an  inflammatory 
process  and  without  the  patient  ever  having  suffered  from  symp- 
toms of  that  condition.  This  is  in  great  probability  the  result  of 
retrogression  and  atrophic  changes  in  the  periosteum  and  in  the 
maxillary  bones.  The  latter  process  leads  to  osteoporosis,  which, 
there  is  good  reason  to  believe,  occurs  in  severe  marantic  cases 
of  diabetes  (see  below),  and  which  is  known  to  occur  in  other 
disorders  of  the  central  nervous  system  {c.  g.,  progressive  par- 
alysis). 

Diabetes  mellitus  does  not  per  se  cause  any  elevation  of  tempera- 
ture. Whenever  fever  takes  place  we  have  to  do  with  some  com- 
plication and  must  make  a  careful  investigation  for  it,  especially  in 
the  lungs.  In  mild  cases  without  complications  the  temperature  is 
normal.  In  severe  marantic  cases  the  temperature  is  below  the 
normal ;  but,  apart  from  coma,  it  is  rarely  below  36°  C.  (96.8°  F.). 
In  the  presence  of  coma  it  sometimes  sinks  several  hours,  or  even 
several  days,  before  death  to  between  25°  and  30°  C.  {j'j'^  and 
86°  R). 


86  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  Nervous  System. 

The  diabetic  patient  is,  as  I  have  mentioned,  often  a  member  of 
a  nervous  or  even  of  a  neurotic  family  in  which,  according  to  the 
two  laws  of  heredity  and  transmutation,  may  be  found  most  of  the 
diseases  that  thrive  on  neurotic  soil.  We  may  thus  find  in  different 
generations  of  the  same  family  slight  mental  disturbances,  developed 
psychoses,  diseases  of  the  brain  and  spinal  cord  alternating  with  ex- 
ophthalmic goiter,  diabetes,  gout,  and  other  morbid  processes,  whose 
dependence  upon  the  nervous  system,  though  not  perfectly  estab- 
lished, is  yet  beyond  doubt. 

Then  it  has  been  ascertained  that  certain  lesions  of  the  nervous 
system  directly  cause  diabetes,  the  symptoms  of  which  develop 
simultaneously  with  the  nervous  symptoms. 

Finally,  it  has  been  learned  in  the  last  few  decades  that  diabetes 
per  se  may  cause  changes  in  the  nervous  elements,  partly  directly, 
partly  through  some  of  its  complications,  and  especially  through  its 
influence  on  the  vessels  of  the  brain  and  consequent  hemorrhage,  as 
well  as  other  circulatory  disturbances. 

Thus,  nervous  disorders — central  and  peripheral,  acute  and 
chronic — are  exceedingly  common  in  conjunction  with  diabetes. 
Among  these  disorders,  however,  neither  the  severe  neuroses  nor 
the  systematic  diseases  of  the  brain  and  spinal  cord  are  at  all  fre- 
quent. Jacoby,  of  New  York,  observed  three  cases  of  epilepsy 
complicated  by  diabetes  mellitus,  and  admits  the  possibility  of  a 
connection  between  the  epileptic  attacks  and  the  diabetic  toxins  in 
the  blood.  Finlayson,  Ebstein,  and  others  also  mention  such  cases  ; 
but  among  nearly  200  diabetics  seen  in  the  course  of  the  last  few 
years  I  have  not  encountered  one  complicated  by  epilepsy.*  Tabes 
dorsalis  and  diabetes  mellitus  have  been  observed  in  the  same  per- 
son in  a  number  of  instances  ;  but  these  and  other  cases  of  diabetes 
occurring  in  conjunction  with  organic,  systematic,  central  nervous 
diseases  constitute  but  a  small  proportion  among  the  large  number 
of  diabetics,  even  if  such  complications  are  found  somewhat  more 
frequently  in  association  with  than  independently  of  the  glycosuric 
dystrophy. 

*In  a  male  child  and  in  some  few  cases  in  womeo  I  have  seen  general  convulsions, 
with  complete  preservation  of  consciousness;  these  I  considered  to  be  hysteric. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  8/ 

A  far  less  rare,  but  still  not  very  common,  expression  of  the 
neurotic  tendency  and  of  a  depraved  state  of  nutrition  is  a  more  or 
less  well  developed  psychoneurosis.  In  Europeans  and  their  de- 
scendants *  this  generally  goes  no  further  than  hypochondriasis. 
Sometimes,  however,  the  patient  presents  a  somewhat  more  pro- 
found mental  change,  and  the  clinical  picture  of  simple  melancholia 
appears.  We  then  generally  find  only  the  mild,  active  form  of  the 
disease,  with  only  moderate  impairment  of  intellectual  activity, 
though  a  certain  degree  of  lack  of  energy  is  found  in  these  as  in  all 
cases  of  melancholia.  Pronounced  apathy,  hebetude,  or  even 
stupor  is  exceedingly  rare,  and  the  same  may  be  said  of  hallucina- 
tions. The  false  ideas  are  rarely  without  some  real  objective  cause, 
and  generally  only  represent  the  hypochondriacal  state  already 
mentioned.  Sometimes,  however,  one  finds  entirely  unfounded 
fixed  ideas,  such  as  are  observed  in  developed  melancholia — e.  g., 
a  delusion  of  poverty  in  the  face  of  excellent  material  circumstances, 
etc.  I  have  also  seen  instances  of  fully  developed  melancholy 
raptus  with  strong  terror  and  violent  tendencies.  Suicide  is  rare, 
even  among  diabetics,  although  somewhat  more  frequent  than 
among  other  persons. 

The  nervous  centers  that  preside  over  the  metabolism  of  carbohydrates  are 
not  the  same  as  those  that  perform  the  highest  mental  functions,  and  the  con- 
nection between  diabetes  and  the  disturbances  of  these  functions  is  most  vague. 
Mild  diabetes  may  be  complicated  by  a  true  psychosis,  and  severe  diabetes 
may  leave  the  mental  state  almost  intact.  On  the  other  hand,  an  influence  on 
the  mind  by  the  diathesis  can  not  be  denied,  and  in  diabetics  of  a  psychopathic 
constitution  hyperglycemia  may  contribute  to  the  development  of  mental  dis- 
ease. An  analogous  influence  is  exerted  by  gout  (Berthier,  Raynor,  Savage, 
Chrichton-Browne).  In  a  mild  but  fully  developed  case  of  melancholia  I  dis- 
covered also  mild  diabetes,  with  1,3  per  cent,  of  glucose  in  the  twenty-four 
hours'  urine  under  ordinary  diet.  A  moderate  restriction  of  the  carbohydrates 
stopped  the  glycosuria  and  was  followed  by  immediate  improvement  in  the 
mental  state,  obvious  to  the  patient's  family.  In  another  case  of  melancholia 
associated  with  diabetes  restriction  of  the  carbohydrates,  with  diminished 
hyperglycemia,  did  not  seem  to  influence  the  melancholia  at  all,  the  patient 
eventually  committing  suicide. 

Other  pure  neuroses  than  hypochondriasis  and  melancholia  are 

*In  the  East  Indian  medical  literature  we  find  statements  from  which  we  may  con- 
clude that  severe  mental  diseases  are  more  frequent  among  diabetic  Hindoos  than  among 
diabetic  Europeans. 


88  DIABETES    MELLITUS    AND    GLYCOSURIA. 

rare  in  association  with  diabetes.  Hysteria — if  properly  distin- 
guished from  purely  neurasthenic  neuroses — is  sometimes,  but  not 
often,  found  in  cases  of  diabetes  (Gumpertz,  Toralbi,  Kleen,  and 
others'). 

Neiirastlienic  symptoms,  both  cerebral  and  spinal,  are  exceedingly 
common  in  diabetics,  and  it  is  rare  to  find  such  a  patient  entirely 
free  from  them.  The  diabetic  is  almost  always  a  wretched  sleeper, 
even  if  polyuria  does  not  disturb  him.  During  the  day  he  suffers 
from  another  neurasthenic  symptom — namely,  drowsiness,  which 
prevents  intellectual  activity  without  inducing  sleep.*  The  slight 
neurasthenic  headache,  almost  continuous,  sometimes  only  felt  as  a 
sense  of  "  emptiness  "  or  of  pressure,  is  frequent.  The  capacity 
for  assiduous  intellectual  work  is  almost  always  diminished  and 
memory  is  often  distinctly  impaired.  Irritability  is  increased,  as 
any  physician  having  much  to  do  with  diabetes  has  learned  at  his 
own  expense.  In  cases  on  the  psychoneurotic  border-Hne  this  may 
amount  to  a  true  "  iracundia  morbosa,"  with  an  unbearable  temper 
and  impulsive,  violent  acts.  Spontaneous  vertigo  is  not  common, 
but  vertigo  at  heights  is  present  in  about  two-thirds  of  all  cases 
with  diminished  power  of  assimilating  carbohydrates.  I  have  also, 
though  rarely,  observed  agoraphobia.  A  host  of  less  important 
neurasthenic  sensory  disturbances,  in  the  form  of  hyperesthesia, 
paresthesia,  and  vague  pains,  annoy  the  diabetic  patient.  Feelings 
of  cold  or  of  heat,  of  the  hair  standing  on  end  or  being  absent,  of  a 
more  or  less  distinct  "casque  neurasthenique,"  of  pressure,  of  creep- 
mg,  of  "  plaque  sacree  "  or  other  rhachialgic  manifestations,  of 
shooting-pains  in  the  limbs,  etc.,  add  to  the  patient's  distress. 
Pains  in  the  epigastrium  are  not  uncommon  in  diabetes,  and  have 
been  compared  to  the  "crises  gastriques  "  of  tabes  dorsalis,  but 
they  seem  hardly  to  be  distinguishable  from  analogous  complaints 
often  made  by  neurasthenic  patients  that  are  not  diabetic. 

Among  neiivalgias  in  diabetes,  sciatica  is  the  most  common. 
Next  in  frequency  come  neuralgias  of  the  fifth  pair  of  nerves 
(trigeminus),  especially  of  the  inferior  maxillary  division.  Supra- 
orbital neuralgia,  aS  in  other  conditions,  is  sometimes  accompanied 


*  An  American  neurasthenic  (nondiabetic)  lady  aptly  described  this  condition  by  say- 
ing :   "I  suffer  from  insomnia  all  night  and  from  somnia  all  day." 


SYMPTOMS   AND   COMPLICATIONS   OF   DIABETES.  89 

by  the  vasomotor  disturbances  that  constitute  migraine.*  All  of 
these  neuralgias,  while  generally  not  very  intense,  are  quite  obsti- 
nate, and  are  often  bilateral. 

In  1887  I  treated  at  Carlsbad  a  case  of  one  of  those  curious  forms  of  aber- 
rant vasomotor  neurosis  that  are  called  equivalents  of  migraine.  The  patient, 
fifty-three  years  old,  was  the  principal  of  a  school.  His  father,  an  uncle,  and 
at  least  one  cousin  had  suffered  from  diabetes.  The  patient  himself  had  suf- 
fered from  the  glycosuric  dystrophy  for  at  least  fifteen,  probably  for  nineteen, 
years,  and  he  had  reached  the  boundary  between  the  mild  and  the  severe 
stage.  He  had  not  had  syphilis,  presented  no  distinct  rigidity  of  the  arteries, 
and  no  other  ocular  disorder  than  moderate  myopia.  From  time  to  time  he 
felt  a  sense  of  rigidity  in  the  left  side  of  the  face,  and  at  the  same  time  paresis 
in  the  left  arm.  I  saw  the  man  during  one  of  these  attacks,  which  had  begun 
at  2  p.  M.  He  presented  marked  paresis  of  the  left  facial  nerve  and  of  the 
whole  left  arm  ;  at  5  p.  M.  his  condition  again  was  perfectly  normal.  Some 
months  afterward  the  patient  suddenly  suffered  a  cerebral  hemorrhage  and  in 
one  of  these  attacks  died  "  apoplectico  modo."  I  presume  that  vasomotor 
neurosis  in  a  case  of  long-standing  diabetes,  with  brittleness  in  the  vessels 
from  diabetic  endarteritis,  is  rather  likely  to  end  this  way. 

Sometimes  there  occur  functional  disturbances  of  the  secretory  nerves,  and 
instead  of  the  customary  decrease  of  secretion  there  may  be  an  abundance,  as 
manifested  by  local  sialorrhea,  hyperidrosis,  etc. 

The  muscular  neurasthenia — not  to  be  confused  with  the  func- 
tional disturbances  resulting  from  marantic  and  other  changes  in 
the  muscles  in  the  severe  cases  —  is  often  marked,  and  even 
in  a  mild  case  the  patient  has  often  much  less  muscular  en- 
durance than  his  general  robust  appearance  would  seem  to  indi- 
cate. Among  other  muscular  neurasthenic  symptoms  there  have 
also  been  observed,  generally  at  night,  cramp  in  the  calves  of  the 
legs,  which  sometimes,  however,  is  not  merely  functional,  but  a 
symptom  of  beginning  inflammation  of  the  posterior  tibial  nerve. 
The  fine,  fibrillary,  clonic  spasm  is  not  uncommon,  especially  in 
the  orbicularis. 

Sexual  potency  is  generally  weakened,  but  the  degree  of  failure 
varies  greatly  and  has  no  fixed  relation  to  the  intensity  of  the  dia- 
betes. This  symptom  often  is  but  little  influenced  by  hypergly- 
cemia, and  is  often  found,  together  with  other  neurasthenic  dis- 
turbances, in  mild  cases,  as  in    cases  of  simple  glycosuria  or  of 

*  That  terrible  cousin  of  the  comparatively  innocent  migraine — epilepsy — is,  in  spite 
of  their  angioneurotic  tendencies,  rare  among  diabetics. 
7 


90  DIABETES    MELLITUS    AND    GLYCOSURIA. 

neurasthenia  without  glycosuria.  In  some  cases,  on  the  other  hand, 
the  patient  is  conscious  of  a  decided  improvement  after  restric- 
tion of  carbohydrates  and  the  disappearance  of  glycosuria.  In  mild 
cases  of  diabetes  the  potency  sometimes  remains  normal  or  nearly 
normal  for  many  years  ;  in  a  small  number  of  cases  apparently  trust- 
worthy patients  make  statements  of  virile  power  that  painfully  strain 
credulity.      Sterility  in  diabetes  will  be  considered  later. 

Diabetic  neuritis  ajtd  poly7ieuritis  *  are  often  detected,  but  still 
more  often  exist  and  escape  detection.  They  certainly  do  not  de- 
pend exclusively  on  the  acetone  and  the  acid  toxins  in  the  blood, — 
the  "  acidosis,"  as  Naunyn  terms  the  condition, — as  they  are  much 
more  common  in  mild  cases  (without  acidosis)  of  long  standing  than 
among  cases  in  the  severe  stage  (with  acidosis),  which  generally  are 
severe  from  an  early  period  of  their  existence  and  rarely  last  many 
years.  In  fact,  the  one  feature  common  to  all  cases  of  diabetes  with 
neuritis  I  have  found  to  be  the  long  duration  of  the  dystrophy.  If 
an  accessory  influence  is  present,  one  may  find  distinct  neuritis  in 
cases  with  an  only  shghtly  impaired  power  of  assimilating  carbohy- 
drates. The  most  frequent  of  these  accessory  influences  are  gout 
and  alcoholism.  Even  in  cases  of  purely  diabetic  neuritis  (without 
gout  or  alcohol)  the  symptoms  are  closely  similar  to  those  of  gouty 
neuritis.  By  this  I  mean  that  diabetic  neuritis,  though  sometimes 
isolated  and  circumscribed  and  sometimes  unilateral,  is  far  more 
often  multiple  and  bilateral ;  that  it  involves  especially  the  lower 
extremities,  though  I  presume  it  may  attack  any  nerve  ;  and,  finally, 
that  it  is  of  a  pronounced  torpid  character.  Only  rarely  does  the 
process  set  in  with  active  symptoms,  acute  pains,  and  sensations  of 
"  tingling."  Usually  its  onset  is  so  insidious  that  the  patient  is 
virtually  unconscious  of  his  sensory  disturbance  until  it  is  disclosed 
by  the  physician's  investigation.  Sometimes,  however,  the  patient 
complains  of  a  feeling  of  burning  or  of  prickling,  and  hyperesthetic 
areas  may  be  found  upon  the  skin.  One  must  not  expect  often  to 
find  distinct  tenderness  of  the  nerves  on  pressure.  Diffuse  muscular 
sensitiveness,  like  that  due  to  rheumatic  infiltration,  is  much  more 

*  Von  Ziemssen  was,  so  far  as  I  know,  the  first  to  point  out  tlie  occurrence  of 
diabetic  neuritis  (1885).  Thomas,  Leyden,  Althans,  v.  Striimpell,  Buzzard,  Charcot, 
Bury  and  Ross,  and  many  others  have  since  contributed  to  our  knowledge  of  this 
subject. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  9 1 

common.  Diminished  sensibility  to  pin-prick,  or  the  esthesimeter, 
or  to  a  tube  filled  with  hot  water  is  frequently  present.  Complete 
analgesia  and  anesthesia  are  exceedingly  rare  ;  I  have  not  seen  a 
single  instance  of  either,  though  cases  so  complicated  are  recorded 
in  literature.     In  rare  instances  I  have  observed  retarded  sensibility. 

Apart  from  the  frequent  spasm  of  the  muscles  of  the  calf,  which 
probably  is  caused  by  neuritis  only  in  rare  cases,  motor  disturbances 
are  much  rarer  than  sensory.  If  the  neuritis  is  intense,  and  there  is 
also  general  debility  and  marasmus,  marked  reaction  of  degeneration 
to  the  electric  current  is  sometimes  present,  and  in  rare  cases  pro- 
found functional  disturbance.  Foot-drop  and  complete  paraplegia 
have  been  observed  in  some  cases,  and  many  instances  of  paresis  or 
paralysis  of  single  muscles  or  of  groups  of  muscles  are  recorded 
(Charcot,  Buzzard,  and  others). 

The  neuritis  often  causes  trophic  changes  within  the  distribution 
of  the  nerve  or  nerves  affected.  Among  such  manifestations  are 
local  hyperidrosis  or  anhidrosis;  atrophic,  thin,  "glossy"  skin; 
cutaneous  eruptions,  as  urticaria,  eczema,  herpes  zoster,  etc.  (see 
below)  ;  discolored,  thick,  brittle  nails,  which  readily  fall  out,  etc. 
The  "  mal  perforant "  and  "Raynaud's  disease"  are  undoubtedly 
manifestations  of  neuritis,  which  probably  also  contribute  to  the 
development  of  other  gangrenous  processes,  whether  occurring  as 
a  single  area  of  sphacelus  or  disseminated  in  patches. 

Absence  or  weakening  of  the  knee-jerk  (and  other  tendinous  and 
cutaneous  reflexes)  is  a  frequent  symptom  of  diabetes.*  The  ex- 
planation for  the  disappearance  of  the  tendinous  and  other  reflexes 
is  to  be  sought  in  changes  in  both  peripheral  and  central  nervous 
elements  (see  below).  Inflammation  of  the  crural  nerve  has  been 
found  in  cases  with  absence  of  knee-jerk.  According  to  Erlen- 
meyer,  the  cause  is  generally  to  be  found  in  changes  in  the  "  ban- 
delettes  externes  "  of  Burdach's  tracts  in  the  posterior  columns  of 
the  spinal  cord.  In  other  cases  postmortem  investigation  has  failed 
to  disclose  any  nervous  change  whatever  (Nonne,  Rosenstein),  and 

*  Absence  of  the  knee-jerk  was  noted  by  Marinian  and  by  Bouchard  in  1884.  It 
occurs  also  in  tabes  dorsalis  and  sometimes  in  apparently  normal  individuals.  This  lat- 
ter occurrence  seems  to  be  much  more  frequent  in  some  races  than  in  others.  Prof.  H. 
C.  Wood,  of  Philadelphia,  has  told  me  that  he  has  found  it  strikingly  often  in  South 
Americans. 


92  DIABETES    MELLITUS    AND    GLYCOSURIA. 

it  seems  possible  that  the  absence  of  the  knee-jerk  may  sometimes 
be  the  result  of  a  purely  functional  disorder,  i.  e.,  a  change  with- 
out discernible  anatomic  basis. 

The  knee-jerk  is  found  absent  in  both  the  mild  and  the  severe 
stage,  but  much  more  frequently  in  the  latter  than  in  the  former. 
Apart  from  this  fact,  absence  of  the  knee-jerk  has  no  distinct  prog- 
nostic significance,  and  it  is  sometimes  found  in  cases  in  which 
the  diabetic  syndrome  has  remained  stationary  in  a  mild  form  for 
many  years.  Often  the  knee-jerk  is  weakened.  Sometimes  it  re- 
mains distinct  for  a  long  time  on  one  side  after  having  disappeared 
from  the  other.  In  some  few  cases  I  have  observed  that  one  or 
both  knee-jerks  have  reappeared  after  having  been  absent  for  some 
time.* 

Statistics  show  that  the  knee-jerk  is  absent  in  from  j.G  to  50  per  cent,  of 
all  cases  of  diabetes.  The  former  figure  is  much  nearer  the  truth  than  the 
latter.  Tests  even  of  the  almost  exclusively  severe  cases  seen  in  hospitals  will 
show  that  the  knee-jerk,  at  least  among  Anglo-Saxon  or  Teutonic  diabetics, 
though  often  weakened,  is  still  distinct  in  the  majority  of  cases.  As  I  write  this, 
an  analysis  of  100  cases  of  diminished  power  of  assimilating  carbohydrates, 
taken  at  random  from  my  records  of  private  practice,  shows  that  the  knee-jerk 
was  absent  in  7  of  39  severe  cases,  in  7  of  51  cases  of  true  though  mild  diabetes, 
and  in  i  case  of  simple  glycosuria  of  many  years'  standing  from  among  10 
similar  cases.  Of  the  85  cases  in  which  the  knee-jerk  remained  distinctly,  it 
was  weakened  in  many  and  in  several  it  was  absent  on  one  side.  When  the 
result  of  the  investigation  was  at  all  uncertain,  the  knee-jerk  has  always  been 
recorded  as  absent. 

The  Other  tendinous  reflexes  and  the  cutaneous  reflexes  may  also 
be  weakened  or  lost.  It  is  important,  however,  to  remember  that 
the  reflex  contraction  of  the  pupil  on  exposure  to  light  is  not  lost 
in  uncomplicated  cases  of  diabetes,  and  the  Argyll- Robertson  pupil 
(contracting  in  accommodation,  but  not  on  exposure  to  light)  points 
to  a  complication  with  central  nervous  diseases  of  organic  origin. 

In  causing  changes  not  only  in  the  peripheral  nerves,  but  also 
in  the  spinal  cord,  especially  its  posterior  columns,  diabetes  mellitus 
sometimes  presents  an  anatomic  similarity  to  tabes.     Diabetes  also 

*  This  may  or  may  not  be  a  favorable  sign.  We  know  that  removal  of  the  influence 
of  higher  centers  is  capable  of  heightening  a  reflex  dependent  on  lower  centers.  In  a 
case  of  diabetes  it  may  happen  that  an  absent  knee-jerk  reappears  after  acute  cerebral 
disturbances  of  paralytic  character. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  93 

is  almost  always  associated  with  more  or  less  pronounced  neuras- 
thenia or  a  group  of  symptoms  sometimes  attended  with  functional 
disturbances  similar  to  those  that  occur  in  tabes.  It  is,  therefore, 
not  astonishing  to  encounter  cases  of  diabetes  presenting  a  cHnical 
picture  that  resembles  more  or  less  closely  that  of  true  tabes.  This 
'^pseudotabes  diabetica,''  like  all  other  forms  of  pseudotabes,  may  be 
attended  with  more  or  less  hyperesthesia,  paralysis,  or  ataxia.  The 
individual  case,  however,  rarely  comports  with  the  somewhat  arti- 
ficial division  of  Leyden,  but  presents  symptoms  of  each  kind. 
Sometimes,  apart  from  true  tabes,  diabetic  patients  present  hyper- 
esthetic  or  anesthetic  areas,  with  peripheral  neurasthenic  pains, 
which,  though  less  violent,  may  resemble  the  lancinating  pains  of 
tabes,  and  be  associated  with  epigastric  pains  that  may  be  mistaken 
for  "  crises  gastriques "  ;  we  further  find  absence  of  tendinous 
reflexes,  sexual  impotence,  a  neurasthenic,  tired,  gait,  or — if  the 
multiple  neuritis  is  pronounced  in  the  lower  extremities — high- 
stepping,  uncertain,  ataxic  movements  of  the  legs  in  walking  and 
an  unsteadiness  in  standing  with  closed  eyes,  much  like  Romberg's 
symptom,  etc.  In  short,  diabetic  cases  of  long  standing  may  ex- 
hibit sensory,  motor,  secretory,  and  trophic  changes  of  various 
kinds,  that  cause  difficulty  in  distinguishing  this  "pseudotabes  peri- 
pherica  diabetica"  from  true  tabes,  especially  from  "  neurotabes 
peripherica."  The  absence  or  the  presence  of  tabetic  ocular  symp- 
toms, which  usually  appear  early  in  true  tabes,  especially  reflex  im- 
mobility of  the  pupils,  may  sometimes  govern  the  decision,  while  in 
other  cases  it  may  be  necessary  to  reserve  the  diagnosis  for  a 
time. 

A  combination  of  diabetes  mellitus  and  true  tabes  is  rare,  but,  apart  from 
being  merely  accidental,  it  may  be  brought  about  by  the  sclerotic  process  of 
tabes  attacking  the  diabetic  center  in  the  floor  of  the  fourth  ventricle  of  the 
brain.  Under  such  circumstances  there  will  (always  ?),  according  to  Guinon  and 
Souques,  be  found :  (i)  anesthesia  within  the  distribution  of  the  trigeminus,  in 
consequence  of  destruction  of  the  center  for  that  nerve,  and  (2)  increased 
frequency  of  the  pulse,  in  consequence  of  destruction  of  the  center  for  the 
pneumogastric  nerve. 

The  question  of  a  connection  between  tabes  dorsalis  and  diabetes  has  been 
most  elaborately  discussed  in  recent  years.  Frerichs,  in  1863,  reported  a  case 
of  tabes  associated  with  diabetes  ;  Smith,  in  1883,  had  a  patient  with  tabes  asso- 
ciated with  glycosuria;  and  Oppenheim,  in  1885,  presented  a  similar  case  to 
the  Society  of  Physicians  of  Berlin.     Absence  of  knee-jerk,  one  of  the  earliest 


94  DIABETES    MELLITUS    AND    GLYCOSURIA. 

symptoms  of  tabes,  has  since  1884  been  noted  in  many  cases  of  diabetes,  while 
from  the  eighties  the  expression  "pseudotabes"  of  Leval-Piquechef  became 
current,  and  our  knowledge  of  the  polyneuritis  of  diabetes  and  of  "pseudo- 
tabes peripherica  diabetica  "  on  the  one  hand,  and  of  "  neurotabes  peripherica  " 
in  true  tabes  on  the  other  hand,  developed.  A  vast  literature  has  grown,  from 
which  I  select  especially  the  names  of  v.  Ziemssen,  Rosenstein,  Lecorche, 
Eichhorst,  Marie  and  Guinon,  v.  Hoesslin,  Price,  Auerbach,  Buzzard,  Leyden, 
Althans,  Charcot,  Auch6,  Burns,  Vergely,  Ross  and  Bury,  Naunyn. 

In  true  tabes  one  rarely  finds  glycosuria.  Eulenburg  observed  one  such 
instance  among  125  cases  of  tabes,  and  Gilles  de  la  Tourette,  3  among  100 
cases,  while  Marie  and  Guinon  found  no  case  of  glycosuria  among  50  of  tabes. 
These  figures  illustrate  the  superficial  character  of  the  investigations,  and 
it  is  certain  that  one  would  find  pathologic  quantities  of  glucose  in  the  urine  in 
a  much  larger  percentage  of  average  individuals  ;  but,  on  the  other  hand, 
these  figures  permit  us  to  draw  the  conclusion  that  the  combination  of  tabes 
and  diabetes  mellitus  is  a  rare  one. 

I  have  seen  a  number  of,  in  part  merely  neurasthenic,  in  part  really 
neuritic,  cases  of  "  pseudotabes,"  but  only  one  case  of  true  tabes  complicat- 
ing diabetes.  This  case  occurred  in  a  clergyman,  sixty-two  years  of  age,  who 
somewhat  feebly  denied  a  history  of  syphilis,  but  who  was  well  known  in  his 
younger  days  to  have  sinned  much  and  indiscriminately  against  sexual  morality. 
This  somewhat  unfaithful  servant  of  the  Church  later  in  life,  after  marriage, 
^and  especially  after  becoming  completely  impotent, — turned  his  iniquitous 
ways  from  the  temple  of  Venus  to  that  of  Bacchus,  and  sometimes  shocked  his 
flock  by  being  terribly  drunk.  Still,  these  triumphs  of  the  flesh,  thanks  to  the 
careful  control  of  his  strong-minded  wife,  caused  such  rare  interruptions  in  an 
otherwise  exceedingly  moderate  mode  of  life,  that  an  alcoholic  basis  for  neu- 
ritis could  be  excluded.  But  there  was  distinct,  though  not  pronounced,  locomo- 
tor ataxia,  with  Romberg's  symptom,  a  feeling  as  if  cotton  were  under  the  feet, 
lancinating  pains  in  the  upper  part  of  the  legs,  absence  of  tendinous  reflexes, 
Argyll-Robertson  pupil,  an  unreliable  sphincter  ani,  and  a  quick  pulse.  The 
urine,  of  normal  quantity,  generally  contained,  with  a  free  diet,  somewhat  more 
than  I  per  cent,  of  glucose.  Not  then  having  in  view  the  publication  of  any 
article  on  diabetes,  I  made  no  more  careful  investigation  than  that  indicated 
by  the  facts  recorded. 

In  advanced  stages  of  diabetes,  or,  rather,  in  cases  of  long  stand- 
ing, when  diabetic  endarteritis  has  had  time  to  render  the  vessels 
brittle,  accidents  from  intracranial  hemorrhage  are  not  uncommon. 
I  believe  that  small  hemorrhages  often  take  place  under  such  con- 
ditions without  causing  symptoms  sufficiently  pronounced  to  attract 
the  notice  of  either  the  patient  or  the  physician,  and  especially  that 
a  number  of  such  hemorrhages  may  take  place  simultaneously 
with  similar  small  ecchymoses  that  occur  in  conjunction  with  hem- 
orrhagic diabetic    retinitis.      In  some  cases  the  patient  may  com- 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  95 

plain  of  deep-seated  pains  in  the  head,  nausea,  ocular  disturbance, 
etc.,  but  the  condition  often  remains  so  vague  and  indistinct  that 
the  physician  is  easily  misled  to  consider  it  an  insignificant  vaso- 
motor disorder,  until  some  serious  accident  directs  attention  to  the 
warnings.  The  patient  may  suddenly  exhibit  apoplectic  symptoms, 
and  subsequently  become  monoplegic  or  hemiplegic,  with  hemian- 
opsia, diplopia,  amblyopia,  strabismus,  ptosis,  etc.  The  nervous 
symptoms  included  in  Weber's  syndrome  have  several  times  been 
observed  in  cases  of  diabetes.  The  oculomotor  nerve  of  one  side  is 
paralyzed,  with  resulting  divergent  strabismus,  crossed  diplopia, 
dilatation  of  the  pupils,  paresis  of  accom.modation,  and  ptosis  ;  while 
on  the  other  side  the  lower  branch  of  the  facial  nerve,  the  arm,  and 
the  tongue  are  paretic  or  paralytic.  In  other  cases  the  abducens  or 
trochlear  nerve  is  paralyzed.  The  paralysis  of  the  facial  nerve  in 
diabetes  is  often  central,  but  not  rarely  is  it  peripheral. 

There  is  one  thing  to  be  said  about  these  diabetic  hemorrhages 
— they  indicate  a  more  favorable  prognosis  than  any  other  kind 
of  cerebral  hemorrhage,  except,  perhaps,  the  syphilitic  ;  I  pre- 
sume because  the  bleeding  often  takes  place  from  quite  small  ves- 
sels. Even  when  the  hemorrhage  has  left  the  patient  unconscious, 
the  symptoms  sometimes  quickly  disappear.  The  patient,  how- 
ever, is  in  constant  danger,  and  a  new  attack  may  bring  life  to  an 
end. 

In  some  cases,  when  a  chronic  nephritis  is  present,  intracranial 
hemorrhage  may  have  to  be  diagnosticated  from  uremia. 

In  autopsies  after  diabetes,  whether  of  the  mild  or  the  severe 
stage,  it  often  happens  that  both  the  naked-eye  and  microscopic 
examination  fail  to  disclose  any  change  in  the  nervous  system. 
This  may  be  so  even  when  neither  the  liver  nor  the  pancreas  is 
materially  altered,  and  when  clinical  observation  has  given  reason 
to  beheve  that  the  glycosuric  dystrophy  has,  as  usual,  been  depend- 
ent upon  nervous  disturbances. 

It  is  proper  to  point  out  that,  on  the  other  hand,  it  is  not  rare  to 
find  postmortem  tumors  and  other  changes  in  the  brain,  which 
must  have  affected  decidedly  the  fourth  ventricle,  without  glycos- 
uria ever  having  been  observed  during  life  (Verron,  Lepine). 

In   autopsies   in   other  cases  of  diabetes  there  are  found  in  the 


96  DIABETES    MELLITUS    AND    GLYCOSURIA. 

central  nervous  system  changes  that  there  is  good  reason  to  con- 
sider as  either  the  cause  or  the  effect  of  diabetes.  From  what  has 
already  been  said,  it  is  generally  easy  to  form  an  idea  as  to  which 
of  the  two  one  has  to  deal  with,  and  it  seems  worthy  of  remark 
that,  in  order  to  cause  glycosuria,  brain-disease  need  not  necessarily 
directly  affect  Bernard's  center  in  the  floor  of  the  fourth  ventricle. 

In  chapter  iii  it  was  mentioned  that  there  have  been  observed  in 
the  brain  after  diabetes  extravasation  of  blood,  atheromatous  pro- 
cesses, aneurysm,  softening,  sclerosis,  colloid  or  fatty  degeneration, 
new  growths  (fibroids,  gliomata,  sarcomata,  osteomata),  and  the 
cysticercus  racemosus,  through  which  Michael's  name  has  become 
familiar  to  all  students  of  diabetes.  It  was  also  pointed  out  that 
general  paralysis  and  akromegaly  have  often,  and  multiple  sclerosis, 
tabes  dorsalis,  paralysis  agitans,  meningitis,  and  syphilitic  disease  of 
the  brain  have  sometimes,  been  seen  in  association  with  either  simple 
glycosuria  or  diabetes. 

A  common  condition  found  after  diabetes  is  dilatation  of  the 
smaller  blood-vessels,  with  small  hemorrhages  into  the  brain 
(Frerichs),  probably  as  a  result  of  changes  due  to  diabetes  endar- 
teritis (see  below).  The  small  cysts  mentioned  by  Saundby  and 
others  are  probably  the  residual  products  of  such  hemorrhages. 

Dickinson,  in  1870,  described  perivascular  spaces  filled  with  detri- 
tus occurring  throughout  the  whole  cerebrospinal  system  in  cases  of 
diabetes.  It  is  a  seductive  theory  to  consider  vasomotor  paralysis, 
or  paresis,  strong  dilatation  of  the  vessels  of  more  or  less  transitory 
character,  and  pressure  with  retrogressive  metamorphosis  of  the 
surrounding  central  nervous  elements  in  the  floor  of  the  fourth 
ventricle,  as  a  cause  of  diabetes  ;  but  the  perivascular  spaces  de- 
scribed by  Dickinson  often  occur  independently  of  diabetes,  and 
neither  German  (Frerichs)  nor  English  (Taylor  and  Goodhart) 
observers  are  inclined  to  ascribe  any  such  significance  to  the  con- 
dition named. 

Glycogen,  which  seems,  in  severe  causes  of  diabetes,  to  be  in- 
creased in  other  organs  as  it  is  decreased  in  the  liver,  has  been 
found  in  much  greater  quantity  than  normal  in  the  brain  after  dia- 
betes (Futterer). 

It  seems  that  diabetes  not  rarely  causes  certain  changes  in  the 
spinal  cord,  the  most  common  of  which  is  sclerosis  of  the  posterior 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  9/ 

columns,  especially  Goll's  and  Burdach's  tracts,  more  rarely  of  the 
lateral  columns  (Williamson,  Leyden,  Minor,  Sandmeyer,  Leich- 
tentritt,  Kalmus,  Hensay). 

Boccardi's  studies  of  the  spinal  cords  in  dogs  made  diabetic  by 
extirpation  of  the  pancreas  have  yielded  valuable  information.  The 
degeneration  is  not  symmetric  and  has  no  systematic  character.  It 
was  found  essentially  in  Goll's  and  Burdach's  tracts  and  in  the  zone 
external  to  them  (Lissauer's  tracts),  close  to  the  posterior  nerve- 
roots.  Sometimes  it  encroached  almost  upon  the  whole  of  the 
posterior  columns,  so  that  only  the  posterior  parts  of  Goll's  tracts 
and  a  thin  zone  of  Burdach's  tracts  remained  free.  Changes  in  the 
lateral  columns  were  much  less  common,  and,  when  present,  were 
found  in  Gowers'  tracts  and  in  the  crossed  pyramidal  tracts. 
Alterations  in  the  sheath  and  in  the  axis-cylinders  of  the  nerves, — 
the  former  being  thinner  and  the  latter  having  a  lacerated  appear- 
ance— were  found  even  a  short  time  after  the  onset  of  severe  dia- 
betes. The  proliferation  of  the  areolar  tissue  and  the  process  of 
sclerosis  began  subsequently.  The  gray  substance  also  was 
changed  ;  degenerated,  enlarged,  hyaline  cells  being  found  in  the 
anterior  and  posterior  cornua  and  in  Clark's  columns,  and  the  nuclei 
of  these  cells  staining  with  difficulty  or  not  at  all.  Here  and  there 
were  observed  lacunae,  Hke  those  described  by  Charcot  and  Joffroy. 
Sometimes  the  endarteritis  with  endothelial  desquamation,  described 
by  Ferraro,  was  noted ;  according  to  Boccardi,  it  was  rather  the 
exception  than  the  rule. 

Nonne  observed  {in  vivo  and  postmortem)  chronic  anterior  polio- 
myelitis as  a  complication  in  a  case  of  severe  pancreatic  diabetes. 

Toward  the  close  of  the  eighties.  Price,  Eichhorst,  and  Auche 
described  diabetic  neuritis,  all  three  finding  parenchymatous  degen- 
erative neuritis  with  uneven,  vacuolar  sheath,  with  the  axis-cylinder 
segmented  or  absent.  It  seems  that  these  alterations  are  present 
most  frequently  in  the  anterior  and  posterior  tibial  nerves.  Hensay 
noted  similar  changes  in  the  facial  and  spinal  accessory  nerves. 
The  crural  nerve  also  has  been  found  in  this  condition.* 

*  The  knee-jerk  in  this  case  had  been  absent  during  life.  Changes  in  the  peripheral 
nerves,  however,  unless  sufficiently  far  advanced  to  destroy  conductivity,  could  not  alone 
cause  loss  of  the  knee-jerk.  Even  though  our  present  means  of  investigation  are  in- 
capable of  detecting  changes  in  the  cellular  nervous  centers,  such  changes  may  exist,  and 


98  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  pneumogastric  7ierve  has  several  times  been  found  abnormal, 
sometimes  sclerotic  and  thickened  (Percy,  Fleury),  sometimes  com- 
pressed by  tumors  (Anger,  Frerichs,  Henrat,  Neumann),  sometimes 
atrophic  from  other  influences  than  tumors  (Lubinoff).  Eichhorst 
found  it  the  seat  of  a  parenchymatous  neuritis. 

The  sympathetic  nervous  system,  which  has  been  studied  care- 
fully, since  it  has  been  known  that  lesions  of  different  parts 
thereof  may  give  rise  to  glycosuria,  has  often  been  found  in  a 
pathologic  condition.  The  changes  have  generally  been  found  in 
the  celiac  ganglion,  and  have  usually  been  of  a  sclerotic,  more 
rarely  of  a  simply  atrophic,  nature. 


Circulatory  System. 

In  inveterate  cases  of  diabetes  the  heart  is  never  very 
strong.  The  sounds  are  often  weak  and  distant,  the  systolic 
elevation  in  the  sphygmogram  being  often  low  and  the  pulse 
uneven,  while  the  patient  complains  of  the  usual  symptoms 
of  weak  heart  if  great  demands  are  made  on  the  circulatory 
apparatus.  This  deficiency  is  usually  present  in  only  a  moderate 
degree,  and  the  pronounced  fatty  heart  is  comparatively  rare. 
Still,  the  fatal  issue  from  this  cause,  by  its  similarity  to  sudden 
death  in  some  cases  of  coma,  has  several  times  contributed  to  the 
number  of  false  reports  of  death  in  coma  apart  from  the  severe 
stage  and  without  "  acidosis." 

The  pulse  varies  exceedingly  in  diabetes.  Its  frequency,  how- 
ever, is  distinctly  increased  in  about  75  per  cent,  of  all  cases  of 
severe  diabetes,  and  it  is  not  rare  in  such  cases,  apart  from 
complications  and  from  diabetic  coma,  to  find  a  pulse  of  100  or 
more.  I  think  this  must  be  caused  by  the  irritating  influence  of 
the  toxins  on  the  heart's  own  sympathetic  centers  more  often  than 
by  any  paralyzing  action  on  the  center  for  the  pneumogastric 
nerve.  If  one  should  speak  of  a  diabetic  type  of  pulse,  it  would  be 
the  small,  feeble  pulse  of  great  frequency. 

Organic  changes  in  the  valves  of  the  heart  are  generally  brought 

may  be  expected  after  the  operation  of  marantic  and  toxic  influences  of  long  standing. 
To  such  changes  may  be  ascribed  both  the  absence  of  the  knee-jerk  and  an  important 
role  in  the  production  of  peripheral  nervous  disturbances. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  99 

about  by  chronic  endarteritic  processes  and  the  aortic  valves  are 
most  commonly  attacked.  Changes  in  the  mitral  valves  do  not  seem 
to  me  to  be  much  more  common  in  association  with  diabetes  than 
independently  thereof,  and  Lecorche's  statistics  showing  such 
changes  in  12.3  per  cent,  of  all  cases  of  diabetes  are  to  me  inex- 
plicable. 

The  most  frequent  macroscopic  alteration  in  the  circulatory  sys- 
tem in  diabetes  consists  in  atheromatous  processes  iQr\(Xmg  to  ai'terio- 
sclerosis  which,  excluding  the  juvenile  cases,  may  be  detected  by 
palpation  during  life  in  about  20  per  cent,  of  all  cases.  It  is  a 
feature  essentially  of  inveterate  cases,  and  is  thus  much  more  com- 
mon in  those  of  long  standing,  though  in  what  I  persist  in  calling 
the  mild  stage,  than  in  cases  that  belong  to  the  severe  stage  and 
rarely  persist  for  any  considerable  number  of  years.  I  should 
think  that  the  glycemia  and  other  blood-toxins  are  responsible  for 
the  condition  ;  but  an  influence  arising  from  enfeebled  vasomotor 
activity  may  possibly  also  contribute  to  the  result.  In  the  presence 
of  pronounced  arteriosclerosis  one  often  finds  alcoholic  or  syphilitic 
complications.  In  rare  cases  the  atheromatous  and  consequent 
conditions  of  the  arteries  of  the  brain  are  not  the  effect  but  the 
cause  of  diabetes. 

Atrophic  ajid  degenerative  conditions  of  the  mj/ocardizim  sometimes 
attend  diabetes,  though  they  are  much  more  rarely  detected  during 
life  than  after  death. 

Much  has  been  said  and  written  about  angina  pectoris  compli- 
cating diabetes.  The  attacks  of  pain  and  the  asthmatic  disturb- 
ances that  sometimes  occur  in  cases  of  diabetes — more  often  during 
the  night  than  by  day,  like  all  sensations  called  angina  pectoris — 
are  either  the  expression  of  organic  disease  of  the  heart,  usually 
resulting  from  changes  in  the  coronary  arteries  and  in  the  myo- 
cardium, or  they  are  manifestations  of  less  important  neuralgic  or 
rheumatic  conditions  in  the  chest-wall,  which,  especially  in  "ner- 
vous "  persons,  may  cause  great  momentary  suffering.  Both  the 
first  kind,  the  true,  dangerous,  "organic"  form  of  angina  pectoris, 
and  the  latter  kind,  the  comparatively  insignificant,  "nervous" 
form  of  pseudo  angina  pectoris,  are  more  common  among  diabetics 
than  among  other  individuals.  In  most  cases  of  diabetes  present- 
ing such   disturbances   that  I  have   seen,  the  attacks   recurring  at 


lOO  DIABETES    MELLITUS    AND    GLYCOSURIA. 

long  intervals  for  years,  the  failure  to  detect  symptoms  of  organic 
disease  on  careful  physical  examination,  the  presence  of  rheumatic 
infiltrations  or  of  neuralgic  symptoms  in  the  chest-walls,  the  differ- 
ence in  the  radiation  of  the  pains  from  what  usually  takes  place 
in  true  angina,  and  the  manifest  influence  of  purely  rheumatic  and 
nervous  causes,  have  led  me  to  attribute  the  symptoms  to  the 
"  nervous "  form,  pseudo  angina,  which  seems  to  me  decidedly 
more  common  than  the  true  angina. 

Among  the  rarer  complications  of  diabetes  there  occur  sometimes, 
though  only  in  advanced  cases,  numbers  of  petechias,  due  to  stnall 
subaitaneous  hemorrhages,  most  frequently  on  the  lower  extremities, 
and  probably  dependent  on  brittleness  of  the  small  vessels  caused  by 
the  diabetic  endarteritis  described  by  Ferraro. 

The  heart,  in  autopsies  of  cases  in  which  there  has  been  pro- 
nounced marasmus,  often  appears  in  a  state  of  brown  atrophy.  In 
other  cases  the  organ  shows  no  distinct  alteration.  In  at  least  1 5 
per  cent,  of  all  cases  some  enlargement,  which  usually  affects  the 
whole  organ,  is  manifest.  Pronounced  fatty  degeneration  is  rare. 
Atheromatous  changes  in  varying  degree  are  common,  but  other 
endocarditis  or  valvular  alterations  are  not. 

Dr.  Jaques  Mayer  found,  clinically,  enlargement  of  the  heart  in  21.6  per 
cent,  of  cases  of  diabetes  in  a  first  series ;  and  in  a  later  series  27  per  cent. 
The  latter  figure  is  nearly  twice  as  high  as  the  15  per  cent,  at  which  I  arrived 
in  the  same  manner — a  difference  that,  as  I  have  found  after  consultations 
with  my  esteemed  colleague,  depends  upon  differences  in  opinion  concerning 
the  physical  basis  for  the  diagnosis.  Dr.  Mayer  himself,  in  an  investigation  of 
the  postmortem  records  of  the  city  of  Berlin,  did  not  obtain  a  higher  figure 
than  13  per  cent.  He  mentions  the  chemic  irritation  of  the  increased  amount 
of  sugar  and  urea  in  the  blood  as  a  cause  'of  the  hypertrophy  without  further 
explanation.  O.  Israel  has  shown  experimentally  that  in  extreme  cases  the 
kidneys  become  unable  to  fulfil  their  function  of  eliminating  urea  and  that  the 
heart  attempts  to  make  good  this  deficiency  by  hypertrophy  of  its  left  ventricle 
(injections  of  sodium  nitrate  and  of  urea  in  horses  and  dogs).  For  my  part,  I 
am  inclined  to  ascribe  the  rather  large  percentage  of  cases  in  which  hyper- 
trophy of  the  heart  attends  diabetes  to  (i)  the  adiposity  which  is  common  in 
diabetes,  and  which  often  per  se  causes  enlargement  of  the  heart;  (2)  the 
atheromatous  changes  in  the  vessels  and  the  obliterating  and  desquamative 
endarteritis  of  the  small  vessels  (Lecorche,  Ferraro) ;  (3)  the  polydipsia  and 
the  increased  quantity  of  water  passing  through  the  system.  The  last  two 
influences  must  increase  the  burden  of  the  heart  and  tend  to  produce  a  work- 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  lOI 

ing  hypertrophy.  In  some  cases  there  coexist  the  causes  of  hypertrophy 
resulting  from  cirrhosis  of  the  kidney,  which,  according  to  the  prevaihng  views 
of  trustworthy  investigators,  consist  in  more  than  the  narrowing  of  the  blood- 
current.  An  irritating  action  of  the  blood-toxins  on  the  vasoconstrictors  might 
especially  be  thought  of.  The  mesenteric  vessels,  however,  which  exert  so 
important  an  influence  on  the  arterial  pressure,  are  in  diabetic  patients  prob- 
ably much  oftener  dilated  than  constricted. 

Diabetic  endarteritis  of  the  small  vessels  (Ferraro,  Strauss,  Boc- 
cardi)  seems  to  be  very  common  and  may  exert  an  important  influ- 
ence in  the  causation  of  hemorrhages  and  of  degenerative  pro- 
cesses in  the  tissues.  It  generally  causes  desquamation  of  the 
endothelium  (Ferarro),  and  sometimes  obliteration  of  the  vascular 
lumen  (Lecorche).  The  brittleness  of  the  small  vessels  in  cases  of 
inveterate  diabetes  is  manifest,  and  finds  expression  in  the  extrava- 
sations into  the  brain,  the  retina,  and  the  cutaneous  and  other 
tissues.* 

Diabetic  blood  presents  distinct  changes  of  a  physical  anatomic 
and  chemic  nature.  To  the  last  I  shall  return  later.  The  per- 
centage of  water  has  been  found  both  increased  and  diminished. 
Von  Jaksch  found  it  diminished  in  every  one  of  lo  cases,  in  which  it 
ranked  from  66.46  per  cent,  upward,  but  never  reached  the  normal, 
72.28  per  cent.  The  specific  gravity  was  found  by  Hammerschlag 
to  be  increased  to  1.064;  by  Davy,  to  be  1.061  ;  by  Nasse,  to  be 
diminished  to  1.048.  The  number  of  red  blood-corpuscles  is 
usually  high  (A.  James  and  others),  except  in  bronze-colored  dia- 
betes (see  below),  in  which  the  number  is  much  diminished,  and 
marked  hemosiderosis,  due  to  the  products  of  disintegrated  red 
blood-corpuscles,  is  found  in  almost  all  of  the  organs.  Bremer, 
Williamson,  and  others  have  found  that  the  red  corpuscles  in  dia- 
betic blood  are  stained  in  a  different  way  by  methylene-blue  and 
other  dyes  than  those  in  normal  blood  (see  below).  Habershon 
found  marked  leukocytosis  in  diabetic  blood,  the   number  of  white 


*  Rosenblath,  as  early  as  1888,  saw  the  walls  of  the  small  vessels  thickened  in  an 
advanced  case  of  diabetes.  The  case  is  surrounded  with  some  interest  on  account  of 
the  presence  of  numerous  small  hemorrhages  or  ecchymoses  strewn  over  the  skin  of  the 
legs.  Above  the  ecchymoses  the  skin  in  many  places  presented  necrotic  areas,  which 
invaded  the  papillary  body  and  about  half  the  depth  of  the  entire  cutis.  The  lungs  con- 
tained circumscribed  gangrenous  areas,  and  the  tongue  and  the  esophagus  were  the  seat 
of  numerous  ulcers. 


I02  DIABETES    MELLITUS    AND    GLYCOSURIA. 

blood-corpuscles  diminishing  with  restriction  of  carbohydrates  and 
increasing  during  coma.  Bettman,  in  a  case  of  diabetes  compli- 
cated by  exophthalmic  goiter,  observed  the  number  of  white  blood- 
corpuscles  undergo  diminution  with  a  free  supply  of  carbohydrates. 
Neusser  found  around  the  nuclei  of  the  leukocytes  in  diabetic 
blood  small  particles  that  stained  black  with  a  modification  of  Ehr- 
lich's  solution  ("perinuclear  basophilia"). 

It  has  been  known  since  the  end  of  the  eighteenth  century  that 
the  blood  of  diabetics  sometimes  exhibits  a  peculiar  whitish  color, 
owing  to  the  numerous  particles  of  fat  present, — diabetic  lipemia, — 
which  may  reach  ii  or  12  per  cent.  (Lecanu,  D.  Gerhardt,  after 
Naunyn).  After  a  rich  meal  the  percentage  of  fat  in  the  blood 
may  reach  high  figures  in  healthy  persons  ;  but  the  lipemia  in 
diabetics,  like  that  which  attends  some  other  pathologic  conditions, 
may  occur  on  an  empty  stomach  (Naunyn).  The  intimate  causes 
of  the  condition  are  unknown.* 


Respiratory  Organs. 

The  most  common  pulmonary  complication  of  severe  diabetes 
mellitus  is  htberculosis.  While  this  pulmonary  disease  ordinarily 
causes  the  sacrifice  of  from  one-seventh  to  one-fifth  of  mankind,  it 
attacks,  according  to  Griesinger,  72  per  cent,  of  diabetics  in  the 
severe  stage  and  destroys  39  per  cent.  These  figures  apply  only 
to  severe  cases,  and  are  never  reached  outside  of  hospitals. 

In  private  practice,  especially  in  watering-places  such  as  Carlsbad, 
the  proportion  of  patients  with  tuberculosis  of  the  lungs  is  a  low 
one  and  the  patients  are  usually  in  a  Hght  stage  and  in  fairly  good 
nutritive  state.  This  observation  would  seem  to  show  that  hyper- 
glycemia predisposes  less  to  pulmonary  tuberculosis  than  does 
marasmus.  It  is  often  said  that  tuberculosis  of  the  lungs  is  much 
more  quickly  fatal  when  associated  with,  than  when  independent  of, 
diabetes ;  but  any  practitioner  with  a  large  number  of  diabetic 
patients  knows  that  the  difference  in  this  respect  between  diabetic 
and  nondiabetic  patients  with  the  same  degree  of  marasmus  is  but 

*  Our  knowledge  of  changes  of  the  blood  in  different  diseases  is  only  developing,  and 
some  of  these  observed  in  diabetic  blood  apparently  do  not  belong  exclusively  to 
diabetes. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  IO3 

slight.  The  results  in  cases  of  pulmonary  tuberculosis  complicating 
diabetes  is  not  rarely  that  usual  with  the  condition  first  named  ; 
but  in  many  of  these  cases,  however,  the  termination  is  that  com- 
mon with  severe  diabetes,  namely,  diabetic  coma. 

Diabetes  mellitus  seems  to  some  extent  to  predispose  to  acute 
croupous  and  lobular  pneumonia,  which,  by  reason  of  the  tendency 
to  severe  complications,  the  weak  heart,  and  the  generally  low  con- 
dition, makes  the  prognosis  worse  than  it  would  otherwise  be. 
Still,  one  ought  not  to  despair  of  a  favorable  issue,  and  I  have  had 
several  diabetic  patients  that  have  passed  through  acute  pneumonia 
— in  one  both  lungs  being  attacked.  When  acute  pneumonia  occurs, 
the  glycosuria  is  generally  diminished  in  a  marked  degree  ;  in  rare 
cases  the  reverse  effect  has  been  observed  (Naunyn). 

Inflammatory  processes  in  the  lungs  in  diabetic  patients,  espe- 
cially in  inveterate  or  advanced  cases,  are  much  more  likely  to 
induce  gangrene  than  in  nondiabetics.  In  Naunyn's  work,  pub- 
lished after  the  Swedish  edition  of  this  book  had  appeared,  the 
great  German  clinician  distinguishes  between  two  forms  of  pul- 
monary gangrene  :  the  acute  and  the  chronic.  I  have  seen  only 
instances  of  the  first,  but  Naunyn  considers  one  about  as  frequent 
as  the  other. 

The  acute  form  generally  begins  as  a  croupous  pneumonia,  and 
is  often  attended  with  hemoptysis  and  abundant  bloody  and  puru- 
lent sputa,  which  generally  lack  the  customary  odor  of  gangrene. 
This  disorder  lasts  at  the  longest  for  a  few  weeks.  After  death 
one  finds  in  the  lungs  gangrenous  and  purulent  cavities,  which 
usually  contain  bacilli  or  other  fungi  (Zenker,  Fiirbringer),  but 
which  often  are  not  very  offensive  to  the  sense  of  smell.  One  of 
my  diabetic  patients,  who  is  still  alive,  recovered  some  years  ago 
from  this  complication.  Marklen  has  observed  a  similar  case.  A 
fatal  issue  is  naturally  the  more  common  termination. 

The  other  chronic  form  of  pulmonary  gangrene  complicating 
diabetes  begins  as  a  catarrhal  condition,  with  fever  and  bloody  or 
purulent,  often  offensive,  sputa,  and  may  last  for  years,  until  hemop- 
tysis or  marasmus  brings  about  a  fatal  issue.  Naunyn  observed 
this  complication  only  in  elderly  patients. 


I04  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Digestive  Organs. 

I  have  already  mentioned  the  diabetic  changes  that  take  place  in 
the  cavity  of  the  mouth.  I  would  here  refer  only  to  the  important 
circumstance  that  in  the  diabetic  the  power  of  viastication  is  likely 
to  be  much  impaired,  on  account  of  caries  or  loss  of  the  teeth. 

The  saliva  is  often  distinctly  diminished,  and  dryness  of  the 
mouth  is  a  common  complaint.  Besides,  the  saliva,  particularly  in 
certain  cases,  is  often  acid  ;  but,  apart  from  the  predisposing  influ- 
ence this  may  have  with  regard  to  caries,  it  is  rather  of  theoretic 
than  practical  interest. 

The  g astro -intestinal  tract  in  diabetic  patients  generally  fulfils  its 
functions  quite  well  so  far  as  digestion  and  absorption  are  concerned, 
and  advanced  changes  are  exceptional. 

A  most  remarkable  circumstance  is  the  rarity  of  distinct  dilata- 
tion of  the  stomach.  One  certainly  finds  often,  clinically  and  post- 
mortem, that  the  Hmits  of  the  stomach  are  rather  extended,  but  not 
beyond  what  may  be  considered  normal ;  and  clinically  pronounced 
dilatation  certainly  does  not  occur  in  one  per  cent,  of  all  cases  of 
diabetes. 

The  diminution  in  all  of  the  secretions  (except  the  urine),  which 
there  is  reason  to  believe  occurs  in  diabetes,  is  not  sufficient  to 
impair  digestion,  and  may,  in  many  cases,  be  made  good  in  the 
stomach  and  the  remainder  of  the  digestive  tract  by  a  hypertrophy  of 
the  secretory  glands  (see  below).  When  I  began  to  make  analyses 
of  the  gastric  juice,  I  made  examinations  in  a  considerable  number 
of  cases  of  diabetes,  but  only  rarely  found  anomalies  of  composi- 
tion or  of  digestive  power.  This  experience  is  in  accord  with  the 
results  obtained  by  Honigmann,  Rosenstein,  Gans,  and  others. 
Numerous  and  exact  investigations  into  the  absorption  of  various 
foods,  as  well  as  careful  fecal  analyses,  also  have  demonstrated  that 
absorption  from  the  gastro-intestinal  tract  is,  as  a  rule,  normal  or 
nearly  normal.* 

Slight  dyspeptic  and  catarrhal  troubles  are,  of  course,  quite 
common  among  diabetics  as  among  other  persons.  During  periods 
in  which  the  use  of  bread  and  vegetables  is  interdicted  or  rigidly 
restricted,    manifest    gastro-intestinal   catarrh,    with    diarrhea    and 

*See  Weintraud's  masterly  treatise  in  "  Bibliotheca  medica,"  i,  Cassel,  1893. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  IO5 

sometimes  with  fetid  stools,  is  especially  prone  to  occur,  and  not 
rarely  necessitates  a  greater  allowance  of  carbohydrates. 

Then  there  is  a  small  class  of  diabetic  patients  who  exhibit  a 
digestive  deficiency  of  a  grave  nature.  These  cases  generally  belong 
to  the  severe,  or  at  least  to  a  very  advanced,  stage  of  diabetes,  and 
depend  upon  primary  or  secondary  degenerative  processes  in  the 
pancreas  or  in  other  glandular  elements  of  the  digestive  apparatus. 

Hirschfeld  *  has  published  seven  such  cases  from  his  own  and  from 
Frerichs'  and  Kiilz's  experience.  In  these,  from  29.4  to  47.2  per 
cent,  of  the  ingested  fat  and  from  30  to  45  per  cent,  of  the  ingested 
proteids  were  found  in  the  feces.  Even  in  these  cases  the  car- 
bohydrates were  fairly  well  digested  and  absorbed.  This  certainly 
does  not  occur  when  the  pancreas  is  in  an  advanced  abnormal  con- 
dition, and  Abelmann  found  in  the  feces  of  Minkowski's  dogs,  after 
extirpation  of  the  pancreas,  almost  the  whole  quantity  of  ingested 
carbohydrates,  upward  of  43  per  cent,  of  the  emulsified  and  nearly 
the  whole  of  nonemulsified  fat,  and  as  much  as  56  per  cent,  of  the 
proteids.  As  a  rule,  the  fat  is  the  kind  of  food  that  most  fre- 
quently and  to  the  greatest  extent  remains  undigested  and  unab- 
sorbed,  even  independently  of  the  great  variations  that  occur  in 
each  individual  case  (Sandmeyer). 

The  deficient  absorption  of  fat,  which  is  apparent  without  closer  investiga- 
tion from  the  hght  color  of  the  feces,  has  long  been  observed  in  diabetes, 
and  has  been  ascribed  to  disease  of  the  pancreas.  Bright,  Eliotson,  Frerichs, 
Fles,  and  Silver  observed  fatty  stools  in  diabetes,  but  their  patients  also  suf- 
fered from  retention  of  bile  and  icterus.  Le  Nobel  noticed  similar  stools  in 
diabetes  without  biliary  retention.  Claude  Bernard,  by  experiment,  came  to 
the  conclusion  that  the  pancreatic  juice  is  necessary  for  the  absorption  of  fat. 
Senn  observed  fatty  stools  after  extirpation  of  the  pancreas.  William  T.  Bull 
and  Hartsen  mark  a  like  observation  in  patients  with  pancreatic  cysts,  and  the 
latter  found  the  extract  with  ether  from  pigeons'  stools  three  times  the  normal 
after  extirpation  of  the  pancreas.    Von  Mering,  Minkowski,  and  Abelmann, 

*See  Hirschfeld's  interesting  paper  in  "  Zeitschrift  f.  klin.  Med.,"  Berlin,  1891.  It 
is  difficult  to  understand  why  these  cases  should  be  described  as  ' '  eine  neue  klinische 
Form  von  Diabetes."  The  absence  of  polyuria  is  not  rare  in  diabetes,  and  in  most 
of  the  seven  cases  the  polyuria,  according  to  Hirschfeld's  own  figures,  was  manifest. 
The  cases  present  no  peculiarity  beyond  the  deficient  digestion,  and  the  establishment  of 
artificial  clinical  forms  is  undesirable.  In  one  of  the  cases,  which  ended  fatally  from 
marasmus,  the  glycosuria  ceased  with  a  strict  diet.  The  pancreas  was  either  carcino- 
matous or  atrophic  or  not  distinctly  changed. 


I06  DIABETES    MELLITUS    AND    GLYCOSURIA. 

finally,  have  observed  analogous  conditions  after  extirpation  of  the  pancreas  in 
dogs.  Thus,  it  is  finally  established  that  pancreatic  juice  plays  an  important 
role  in  the  absorption  of  fat.  It  is  also  known  that  the  pancreas  is  in  some 
way  necessary  to  prevent  hyperglycemia,  and  that  the  destruction  of  this  organ 
is  followed  by  glycosuria.  It  has,  however,  not  been  shown  that  every  diabetic 
patient  who,  apart  from  retention  of  bile,  does  not  digest  fat  suffers  also  from 
disease  of  the  pancreas  ;  while,  on  the  other  hand,  it  is  positively  known  that 
this  organ  may  be  greatly  changed  without  noteworthy  impairment  in  the  ab- 
sorption of  fat  (Hartsen,  Fr.  Miiller)  and  without  diabetes  resulting  (Minkowski). 
It  is  known,  further,  that  there  are  sometimes  in  cases  of  diabetes  reasons  un- 
connected with  the  pancreas  for  digestive  deficiency. 

Habitual  constipation  is,  in  consequence  of  marasmus,  and  an 
atonic  state  of  the  bowels,  deficient  innervation,  etc.,  still  more 
common  among  diabetics  than  among  other  individuals,  and  any 
tendency  in  that  direction  is  likely  to  become  manifest  with  rigid 
restriction  of  carbohydrates. 

In  connection  with  a  consideration  of  the  digestive  apparatus  in 
diabetics  illustrations  are  not  wanting  of  the  great  frequency  of 
purely  nervous  symptoms  in  association  with  the  diabetic  syn- 
drome. Gastro-intestinal  7ieuroses  are  exceedingly  common  among 
diabetic  patients.  It  would  carry  me  far  beyond  my  purpose — as 
it  would  be  beyond  my  power — to  describe  here  all  of  the  different 
neuroses  of  this  kind  that  may  occur  in  diabetes.  The  most  fre- 
quent of  these  belong  to  that  group  of  which  a  part  generally  is 
called  nervous  dyspepsia  or  gastric  neurasthenia,  but  which,  on 
account  of  its  manifold  sensory  and  motor  disturbances,  referred  to 
different  parts  of  the  digestive  tract,  I  prefer  to  designate  gastro- 
intestinal neurasthenia.  The  patient  often  suffers  from  inexplicable 
variations  in  appetite, — which  may  one  day  be  excellent  and  the 
next  fail  entirely, — from  eructations,  a  sense  of  pressure,  of  tension, 
or  of  pain  in  the  epigastrium,  or  of  nausea,  etc.  Sometimes  flatu- 
lence is  the  chief  complaint.  Easily  aroused  and  excessive  peris- 
taltic activity  may  cause  attacks  of  diarrhea  on  slight  provocation  ; 
spastic  disturbances  of  stomach  and  intestines  may  cause  severe 
pains,  and,  especially  in  the  latter,  may  give  rise  to  what  Kussmaul 
calls  "  tormina  ventosa."  One  sometimes  may  find  a  part  of  the 
alimentary  canal  distended  by  gas  and  giving  for  the  moment  the 
impression  of  a  tumor.  I  believe  that  the  much-talked-of  diabetic 
crises  gastriques  usually  are  of  spastic  nature.      They  may  be  quite 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  lO/ 

painful  and  be  followed  by  diarrhea,  and  in  rare  cases  by  vomiting. 
I  can  not  find  that  they  differ  from  similar  manifestations  in  purely 
neurasthenic  cases,  and  they  certainly  resemble  these  more  nearly 
than  the  tabetic  "  crises  gastriques,"  to  which  they  have  been  com- 
pared. 

Secretory  neuroses  certainly  exist  much  oftener  than  they  are 
noted,  being  sometimes  difficult  of  detection,  even  on  elaborate  in- 
vestigation. I  have  twice  seen  in  diabetic  patients  what  I  believed 
to  be  an  excessive  secretion  of  gastric  juice,  a  condition  that  is  sel- 
dom mentioned.  The  glycosuric  dystrophy  is  rather  hkely  to 
diminish  the  secretions,  but  an  exception  in  the  other  direction  may 
occur  with  the  gastric  juice,  just  as  sometimes  hyperhidrosis  is 
observed  instead  of  the  customary  anhidrosis.  Hyperacidity  (from 
hydrochloric  acid)  has  sometimes  been  noted  (Riegel,  Naunyn).  I 
believe  that  it  is  not  uncommon. 

The  most  serious  of  all  gastric  neuroses  that  can  attack  the  dia- 
betic patient  is  nervous  anorexia  (Gull,  Lasegue),  which  is  some- 
times found  in  neuropathic  persons,  but  which,  happily,  is  rare  both 
in  association  with  and  independently  of  diabetes.  In  the  few 
cases  other  than  of  diabetes  in  which  I  have  encountered  this 
curious  affection — which  has  Kttle  in  common  with  the  refusal  to 
eat  in  developed  mental  diseases — the  course  has  been  favorable, 
and  the  patients,  after  a  few  weeks  of  marked  inanition,  have  been 
restored  to  normal  appetite  and  health.  This  seems  also  to  have 
been  the  almost  universal  rule  in  recorded  cases.  In  diabetic 
patients,  however,  the  prognosis  appears  to  be  much  less  favorable. 
The  anorexia  is  sometimes  particularly  obstinate,  and  is  especially 
pronounced  with  regard  to  meat  and  fat,  and  even  if  the  patient  is 
allowed  a  completely  unrestricted  diet, — which,  I  think,  is  to  be 
recommended, — all  remedies  may  fail  to  secure  the  ingestion  of 
more  than  a  small  part  of  the  food  required  for  the  genera- 
tion of  the  necessary  number  of  calories.  Most  of  these  patients 
are  women.  The  last  one  under  my  care  exhibited  after  the  begin- 
ning of  the  anorexia  no  glycosuria,  but  pronounced  diaceturia 
from  the  inanition,  and  died  after  several  months  of  marasmus. 

Gastro-intestinal  changes  have  often  been  found  after  death, 
though  they  are  rarely  of  a  marked  nature.      The  increased  diges- 


I08  DIABETES    MELLITUS   AND    GLYCOSURIA. 

tive  demand  causes  at  first  functional  hypertrophy  in  different 
structures.  Dittrich,  Frerichs,  Lancereaux,  Rosenstein,  and  others 
found  hypertrophy  of  the  muscular  layers  in  the  stomach.  Boccardi 
saw  (in  diabetic  dogs)  enlargement  of  the  gastric  glands  and  their 
ducts,  and  dilatation  of  the  lymphatic  vessels.  [Hyperacidity  of  the 
gastric  juice — 0.4  per  cent. — is  not  rare  (Riegel).]  Boccardi  also 
found  Brunner's  glands  and  Lieberkiihn's  crypts  hypertrophied. 
I  have  generally  found,  both  clinically  and  after  death,  a  rather 
large,  but  never  decidedly  dilated,  stomach.  I  have  several  times 
on  postmortem  examination  seen  enlargement  of  the  mesenteric 
glands,  as  first  pointed  out  by  Frerichs. 

In  advanced  cases  there  is  atrophy  both  of  the  muscular  (Fre- 
richs) and  of  the  glandular  elements  (Ferraro,  Boccardi).  Armanni 
found  in  one  of  Cantani's  patients  pronounced  atrophy  of  the 
peptic  glands.  Rosenstein  mentions  a  decreased  amount  of  hydro- 
chloric acid.  These  changes  and  those  that  sometimes  occur  in  the 
pancreas  suffice  to  explain  the  severe  digestive  troubles  in  Hirsch- 
feld's  cases,  previously  mentioned.  Catarrhal  changes  are  exceed- 
ingly common. 

Hemorrhage  and  ulceration  are  mentioned  as  occurring  in 
different  parts  of  the  gastro-intestinal  tract  (Frerichs,  Ferraro,  and 
others). 

The  pancreas  plays  a  most  important  part  in  the  pathogenesis 
of  diabetes  mellitus,  and  I  propose  further  on  to  describe  pan- 
creatic diabetes  and  to  give  a  summary  of  v.  Mering's  and  Mink- 
owski's discovery  of  the  results  of  extirpation  or  resection  of  the 
pancreas. 

Clinically,  anything  noteworthy  with  regard  to  the  pancreas  is 
found  with  comparative  rarity  among  diabetic  patients.  As  I 
write,  it  happens  that  I  have  under  observation  such  a  case,  in  which 
the  rapid  development  from  day  to  day  is  striking.  The  patient,  a 
Jewess,  sixty-seven  years  old,  has  had  upward  of  six  per  cent,  of 
glucose  in  her  urine,  the  sugar  disappearing  entirely  with  restriction 
of  diet.  In  the  beginning  of  the  diabetes,  which  set  in  quite  sud- 
denly, there  was  no  diacetic  acid  in  the  urine.  Now,  Gerhardt's 
reaction  is  pronounced  as  a  result  of  inanition.  The  patient  is 
often  ravenously  hungry,  but  can  scarcely  take  any  food  when  it 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  IO9 

is  brought  to  her.  She  sometimes  vomits,  and  complains  often  of 
severe  pains  in  the  epigastrium  and  in  the  back.  Palpation  raises  a 
suspicion  of  increased  resistance  over  the  head  of  the  pancreas. 
No  icterus  is  present,  but  a  decided  cachectic  hue.  The  feces  some- 
times contain  large  quantities  of  fat.  Unfortunately,  I  shall  not 
be  able  to  be  present  at  the  postmortem  examination,  which  is  cer- 
tain to  take  place  within  a  few  weeks,  and  which  probably  will 
reveal  a  carcinoma  of  the  pancreas.* 

Since  the  connection  between  diabetes  and  disease  of  the  pan- 
creas was  pointed  out  that  organ  is  as  much  studied  in  diabetic 
patients  after  death  as  it  was  neglected  in  the  past.  Such  changes 
in  the  pancreas  as  can  be  reasonably  considered  to  have  caused  the 
diabetes  are,  however,  found  comparatively  rarely — certainly  not  in 
more  than  ten  per  cent,  of  all  autopsies  after  diabetes.  In  fully 
ninety  per  cent,  or  more  of  such  cases  the  pancreas  is  either  normal 
or  diminished  in  size  and  flabby  in  consistence,  with  small  but 
otherwise  normal  acini ;  it  presents  a  condition  of  simple  atrophy, 
which  may  with  much  better  reason  be  considered  an  effect  than  a 
cause  of  the  glycosuric  dystrophy,  f 

Among  the  comparatively  few  cases  in  which  disease  of  the  pan- 
creas may  be  considered  as  a  cause  of  the  diabetes  the  most  com- 
mon are  atrophy  and  cirrhosis  from  the  presence  of  calculi  in  the 
ducts,  which  may,  in  consequence,  be  much  enlarged. 

Cirrhosis  of  the  pancreas,  interstitial  pancreatitis,  may  also  exist 
without  the  presence  of  calculi  (Heinemann),  and  in  exceptional 
cases  may  cause  diabetes. 

Sometimes  the  pancreas  is  the  seat  of  more  or  less  fatty  necrosis, 
as  I  have  seen  in  cases  in  which  the  whole  clinical  picture  has  been 
that  of  fat,  constitutional,  gouty,  nonpancreatic  diabetes.  Seyler 
recently  recorded  a  case  of  ischemic  fatty  necrosis,  which  he  con- 
sidered due  to  atheromatous  processes  that  were  exceedingly  pro- 
nounced in  the  celiac  axis  and  its  branches,  with  diabetes  as  a 
remote  sequel. 

*  Since  this  was  written  the  diagnosis  has  been  found  to  be  correct.  It  is  a  curious 
fact  that  the  woman's  father  also  died  of  carcinoma  of  the  pancreas. 

f  My  opinion  in  this  respect  is  based  upon  not  a  few  personal  autopsies  and  on  infor- 
mation gained  in  Carlsbad,  where  a  considerable  number  of  postmortem  examinations 
after  diabetes  are  made. 


no  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Some  observers  mention  interstitial  lipoma  of  the  pancreas 
(Hansemann,  Naunyn). 

Hyaline  necrosis,  with  homogeneous,  transparent  contents  in  the 
enlarged,  glandular  cells,  such  as  has  been  described  by  Armanni 
in  the  kidneys  (see  below),  seems  also  sometimes  to  occur  in  the 
pancreas  (Saundby). 

Carcinoma  of  the  pancreas  has  several  times  been  found  after 
diabetes,  and  is  now  and  then  diagnosticated  during  life.  It  may 
exist  without  diabetes,  partly  because  a  sufficient  amount  of  the 
glandular  tissue  is  left  intact,  partly,  as  Hansemann  points  out, 
because  of  the  retention  by  the  degenerated  cells  of  some  of  their 
functional  capability. 

Other  changes  in  the  pancreas  are  rare.  Abscess  has  been 
found,  but  seems  only  exceptionally  to  have  time  before  death  to 
cause  diabetes.  Cysts  generally  leave  enough  of  normal  tissue  to 
prevent  the  development  of  diabetes.  Frerichs  has  reported  a  case 
in  which  the  postmortem  findings  seem  to  indicate  the  development 
of  diabetes  as  a  result  of  (Fitz's)  hemorrhagic  acute  pancreatitis  ; 
Benda  and  Stadelmann  have  reported  a  similar  case.  The  majority 
of  instances  of  acute  hemorrhagic  pancreatitis  are  unattended  with 
glycosuria  (Seitz). 

Hansemann  *  has  recently  published  an  excellent  paper  on  the  relations  of 
the  pancreas  to  diabetes.  He  believes — on  insufficient  grounds,  it  seems  to 
me — in  the  occurrence  of  a  specific  variety  of  diabetic  atrophy  of  the  pancreas, 
and  maintains  that  there  exist  anatomic  difTerences  between  this  and  a  simi- 
lar state  after  nondiabetic  cachexia  or  marasmus. 

The  liver  is  the  organ  in  which  one  must  look  for  the  immediate 
cause  of  diabetes  if,  with  Bernard  and  his  many  adherents,  one 
considers  the  condition  to  depend  upon  an  excessive  production 
of  sugar.  We  have  already  seen  that  a  number  of  affections  of 
the  liver  are  sometimes,  though  inconstantly,  accompanied  by 
glycosuria,  which  may  or  may  not  be  found  after  ligation  of  the 
gall-ducts,  or,  together  with  biliary  fistulse,  after  attacks  of  gall- 
stones, after  trauma  over  the  liver  in  association  with  pylethrom- 
bosis,  organic  heart-disease  and  a  consequent  stasis  in  the  liver, 
acute  yellow  atrophy,  phosphorus-poisoning,  amyloid  degeneration, 

*"Zeitschr.  f.  klin.  Med.,"  1894. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  I  I  I 

and,  above  all,  cirrhosis.  I  consider  the  frequency  of  the  associa- 
tion of  cirrhosis  of  the  liver  and  glycosuria  fully  demonstrated  since 
Naunyn,  in  his  excellent  work  recently  published,  mentions  22 
cases  of  incipient  and  2  cases  of  advanced  cirrhosis  of  the  liver 
among  152  diabetics. 

Still,  it  must  not  be  expected  that  some  distinct  abnormity  of 
the  liver  will  be  found  clinically  in  a  large  percentage  of  diabetic 
patients.  The  character  of  Naunyn's  figures  depends  on  the 
enormous  frequency  of  cirrhosis  of  the  liver  in  and  around  Stras- 
burg,  where  his  observations  were  made  ;  his  earlier  figures  are 
much  lower.  The  usual  state  of  the  liver  is,  so  far  as  clinical 
investigation  goes,  a  normal  one.  On  percussion  the  size  of  the 
organ  is  found  to  be  within  the  normal  limits,  and  palpation  yields 
no  information  of  any  change  in  form,  consistency,  or  sensibility. 
In  other  cases,  fewer  though  not  very  rare,  there  is  some  enlarge- 
ment and  perhaps  some  tenderness  on  pressure.* 

Now  and  then  any  one  who  sees  many  diabetic  patients  will  find 
one  with  a  cirrhotic  liver — generally  of  the  usual  atrophic  variety. 
I  will  cite  two   cases   under   observation  within  the  last  few  years  : 

Dr. ,  a  Scandinavian,  is  an  unmarried  physician,  fifty-four  years  old, 

who  has  a  great  aversion  to  pure  water.  He  does  me  the  honor  to  consult  me  in 
Carlsbad,  where  he  appears  in  my  office  with  watery  eyes,  a  rough  voice,  trem- 
bling hands,  and  a  flabby  panniculus,  and  complains  bitterly  of  loss  of  appetite 
and  nausea,  especially  in  the  mornings,  etc.  When  he  discovers  that  I  have, 
without  asking  any  unpleasant  questions  or  making  further  investigation, 
booked  him  as  a  case  of  chronic  alcoholism,  he  indignantly  protests,  exclaim- 
ing that  he  has  drunk  "  only  "  a  bottle  of  claret  and  half  a  bottle  of  whisky  a 

*Glenard,  of  Vichy,  has  arrived  at  other  conclusions  in  his  "  Resultats  Objectifs 
d'Exploration  du  foie  chez  les  Diabetiques,"  Paris,  1890.  Among  324  diabetics  he  found, 
on  palpation,  by  a  method  that  he  designates  "  precede  du  pouce,"  a  distinct  change  in 
60  per  cent. ,  and  these  cases  he  classifies  under  8  varieties  and  42  subvarieties,  which 
he  illustrates  by  diagrams.  So  far  as  both  classification  and  palpation  go,  this  is  entirely 
beyond  me,  as  well  as  some  others.  The  last  medical  friend  to  whom  I  showed  Glenard's 
plate  did  as  Voltaire's  governor — "  il  releva  sa  moustache  et  sourit  am^rement,"  but  said 
nothing.  Neither  will  I  concede,  without  all  reservation,  the  truth  of  Glenard's  state- 
ment :  tout  foie  percu  par  la  palpation  chez  le  vivant  est  un  foie  anormal.  Glenard  con- 
siders hypertrophy  of  the  liver  to  be  present  in  34.5  per  cent,  of  all  cases  of  diabetes, 
and  usually  limited  to  the  right  lobe ;  the  consistency  to  be  increased  in  one-third  and 
sensitiveness  in  one-fourth  of  all  cases  ;  and  nontender  induration  to  be  present  in  23  per 
cent,  of  all  cases  and  in  40  per  cent,  of  those  in  which  the  liver  can  be  felt  by  palpa- 
tion. 


112  DIABETES    MELLITUS    AND    GLYCOSURIA. 

day.  Even  this  concession  probably  represents  only  a  part  of  the  truth. 
Syphilis  was  denied. 

The  radial  and  the  temporal  arteries  were  sclerotic.  The  heart  was 
somewhat  enlarged  in  all  directions  ;  the  second  aortic  sound  somewhat  accent- 
uated. On  percussion  the  right  lobe  of  the  liver  appeared  to  be  distinctly 
diminished  in  size,  but  there  was  no  tenderness.  The  spleen  was  a  little 
enlarged.  There  was  no  icterus,  no  bile  in  the  urine,  and  no  manifestations 
of  stasis.  The  tongue  and  the  breath  were  fairly  normal ;  only  a  few  teeth 
remained,  and  those  were  carious. 

The  patient  was  irritable,  slept  badly,  and  could  not  approach  steep  declivi- 
ties.    Sexual  power  was  "  highly  satisfactory."     The  knee-jerks  were  normal. 

When  the  patient  received  about  120  grams  of  starch  with  his  food,  he 
passed  1700  cu.  cm.  of  urine  of  a  specific  gravity  of  1.019  and  containing  a 
trace  of  albumin  and  about  0.05  per  cent,  of  glucose.  On  microscopic  exami- 
nation quite  a  remarkable  number  of  calcium-oxalate  crystals  were  found,  and 
only  a  few  hyaline  casts.  Single  samples  of  the  urine  contained  as  much  as 
0.5  per  cent,  of  glucose.     Glycosuria  was  first  observed  fourteen  years  ago. 

The  patient  died  about  a  year  after  my  examination,  and  I  received  word 
that  the  liver  was  fairly  well  advanced  in  cirrhosis. 

Mr. ,  a  Jewish  Bavarian  brewer,  thirty-nine  years  old,  whose  father  had 

been  a  diabetic  and  who  himself  had  always  been  "  nervous,"  forgot  the  law 
and  the  prophets  and  the  usually  temperate  Jewish  customs,  drank  for  many 
years  much  "  Kornbranntwein  "  and  beer,  smoked  ten  cigars  a  day,  and  was 
far  from  moderate  "in  puncto  sexus."  He  insists  that  he  never  had  syphilis. 
Two  years  ago  he  began,  from  mere  thirst,  to  attack  the  beer-casks  even  more 
energetically  than  before,  and  his  physician  found  four  per  cent,  of  glucose 
in  the  urine.  Since  then  the  patient  has  lived  under  a  moderate  restriction  of 
carbohydrates. 

The  man  was  exceedingly  neurasthenic,  and  had  a  "  smoker's  heart."  The 
reflexes  were  normal.  The  breath  was  natural ;  one  tooth  was  missing,  and  the 
remainder  presented  very  little  caries.  The  liver  was  somewhat  reduced  in  size. 
The  left  lobe  was  distinctly  palpable.  The  spleen  extended  a  little  beyond  the 
anterior  axillary  line.  Slight  icterus  existed.  About  120  grams  of  carbo- 
hydrates caused  scarcely  0.5  per  cent,  of  glucose  to  appear  in  the  daily  2500 
cu.  cm.  of  urine,  with  a  specific  gravity  of  1.016  and  containing  a  trace  of 
albumin. 

I  have  already  mentioned  the  frequency  with  which  gall-stones 
complicate  diabetes  mellitus. 

On  postmortem  examination  the  liver  often  appears  normal  to 
the  naked  eye  and  on  microscopic  examination.  In  other  numer- 
ous cases  the  liver  is  slightly  enlarged,  probably  as  a  result  exclu- 
sively of  dilatation  of  the  vessels.  The  hyperemia  is  of  the  active 
kind.     The  veins  usually  are  not  distended,  but  the  arteries  and 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  I  1 3 

capillaries  are  distinctly  so,  and  the  organ  presents  a  more  or  less 
rosy  color,  often  limited  to  certain  parts.  In  some  cases  the  vessels 
may  be  dilated  "  ex  vacuo  "  as  a  result  of  atrophy  of  the  Hver-cells 
(Armanni).  Now  and  then  one  finds  what  Hanot  has  described  as 
a  liver  "  couleur  chamois,"  with  a  reddish-yellow  color,  and  the 
intralobular  veins  distended.  Simple  atrophy,  with  diminution  in 
size  and  a  brownish-yellow  color,  is  not  rare.  The  same  can  be 
said  of  the  typical  fatty  liver.  Under  these  conditions  the  gly- 
cogen, which  is  always  likely  to  be  diminished,  especially  in  cases 
of  severe  glycosuric  dystrophy,  reaches  its  lowest  figures  (Boc- 
cardi).  Cirrhosis,  moderately  developed,  is  not  rare,  but  rarer  than 
any  of  the  other  states  mentioned.  Abscess,  probably  somewhat 
more  frequent  in  association  with  than  independently  of  diabetes, 
is,  nevertheless,  quite  exceptional.  When  the  fatal  issue  has  been 
immediately  preceded  by  high  fever,  the  parenchymatous  change 
designated  by  the  Germans  as  cloudy  swelling  is  found  in  cases  of 
diabetes,  as  under  other  conditions. 

Boccardi  observed  in  dogs,  after  extirpation  of  the  pancreas, 
hyperemia  of  the  liver,  but  no  true  hypertrophy.  Atrophy  or 
fatty  degeneration  quickly  came  on.  While  the  nucleus  remains 
perfectly  visible,  vacuoles  are  discernible  in  the  protoplasm,  as  after 
arsenical  poisoning  (Steinhaus,  Gianturco,  Sampacchia).  The  vessels 
become  markedly  dilated,  partly,  at  least,  in  consequence  of  an  in- 
fluence "  ex  vacuo  ";  and  small  hemorrhages  occur,  especially  near 
the  surface.  Boccardi  found  also  in  the  liver  diabetic  desquamative 
endarteritis,  but  not  the  hyaline  necrosis  observed  in  the  spinal  cord 
(Boccardi),  in  the  kidneys  (Armanni),  in  the  pancreas  (Saundby), 
and  in  the  liver  (Ferraro). 

Roque,  Devie,  and  Hugonenq  found  here  and  there  among  the  liver-cells 
crystals  which  they  believed  to  be  leucin  or  tyrosin. 

Bonome,*  after  extirpation  of  the  celiac  ganglion,  noted  neuro- 
paralytic dilatation  of  the  vessels  and  hemorrhage  and  atrophy  of 
the  lobules  ;  i.  e.,  a  state  similar  to  which  Boccardi  found  in  the 
liver  of  dogs  after  extirpation  of  the  pancreas. 

The  spleen  may  be  mentioned  here  on  account  of  its  relation  to 

*  "  Riforma  Med.,"  1842. 


I  1 4  DIABETES    MELLITUS    AND    GLYCOSURIA. 

the  liver.  It  is,  like  all  the  abdominal  organs,  often  hyperemic  and 
somewhat  enlarged.  Clinically,  distinct  enlargement  is  of  import- 
ance, as  it  may  strengthen  a  doubtful  diagnosis  of  incipient  cirrhosis 
of  the  liver.  In  advanced  diabetic  marasmus  the  spleen  is  often  small 
and  flabby,  and  it  participates  in  the  general  atrophy. 


Urinary  Organs. 

The  kidneys  are  often  slightly  changed  in  diabetes,  but  compara- 
tively rarely  show  excessive  alterations. 

Fully  a  third,  perhaps  more,  of  all  diabetic  patients  show  albu- 
minuria. The  albumin  in  most  cases  is  present  only  in  traces,  or 
at  least  in  small  quantities,  and  it  usually  does  not  reach  so  much 
as  one  part  in  a  thousand.  Almost  all  patients,  who  have  lived 
for  some  time  within  the  severe  stage,  present  some  albumin- 
uria, which  in  the  mild  stage  occurs  only  in  a  small  minority  of 
cases. 

Slight  albuminuria  in  a  diabetic  patient  is  usually  considered  of 
less  clinical  and  prognostic  significance  than  under  other  conditions; 
and  in  the  presence  of  conflicting  therapeutic  indications,  as  between 
the  kidneys  and  the  glycosuric  dystrophy,  physicians  generally 
regard  chiefly  the  latter.  In  some  cases  the  albuminuria  is  an 
effect  of  stasis  in  the  kidneys  from  the  weakness  of  the  heart  that 
is  common  among  diabetics.  In  cases  that  have  reached  the  severe 
stage  it  is  often  undoubtedly  of  toxic  origin,  resulting  from  the 
irritation  of  the  kidneys  in  consequence  of  the  "  acidosis."  Arterio- 
sclerosis per  se  also  not  rarely  causes  some  degree  of  albuminuria 
without  the  presence  in  the  urine  of  epithelial  elements  from  the 
kidneys  ;  such  vascular  changes  are  likely  to  be  found  earlier  in 
life  in  diabetics  than  is  usual  in  others.  Further,  true  nephritis  is 
not  rare  in  diabetes.  As  Grube  correctly  remarks,  it  is  usually  a 
form  of  mixed  parenchymatous  and  interstitial  character  ;  casts  can 
then  usually  be  found  without  difficulty  in  the  urine.  (From  the 
presence  in  the  urine  of  hyaline  casts  no  conclusions  as  to  more 
profound  alterations  are  to  be  reached,  as  such  formations  are 
extremely  common,  especially  in  senile  individuals,  in  connection 
with  or  independently  of  true  nephritis.)  The  typical  gouty 
kidney  is  occasionally  found.     It  sometimes  causes  no  albuminuria, 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  II 5 

but  only  polyuria,  the  urine  being  of  low  specific  gravity,  and 
containing  only  small  quantities  of  glucose. 

Like  almost  all  writers  on  diabetes,  I  have  a  number  of  times 
observed  the  curious  change  in  the  glycosuria  that  takes  place  in 
cases  with  cirrhotic  processes  in  the  kidneys.  As  the  arterial 
pressure  and  the  quantity  of  the  urine  increase  and  the  specific 
gravity  falls  with  the  advancing  cirrhosis,  the  glycosuria  ceteris 
paribus  slowly  but  quite  considerably  grows  less  marked.  The 
same  patient  that  in  the  incipient  stage  of  interstitial  nephritis  with 
a  fixed  supply  of  carbohydrates  excreted  twenty  grams  of  glucose 
in  the  twenty -four  hours,  may  five  years  afterward,  under  the  same 
conditions,  excrete  only  one  gram  of  glucose.  Such  cases  may 
finally  resemble  the  rare  combination  of  diabetes  insipidus  with 
insignificant  but  pathologic  traces  of  glucose  in  the  light,  abundant 
urine.  The  state  of  the  glycemia  in  these  cases  can  not  at  present 
be  considered  settled,  and  the  result  of  injections  of  phloridzin 
in  patients  with  interstitial  nephritis  is  still  uncertain  (Klemperer 
versus  Magnus-Levy,  Naunyn,  and  others).  Naunyn,  in  his  recent 
work,  expresses  the  opinion  that  the  curious  increased  tolerance 
for  carbohydrates  in  cases  of  diabetes  complicated  with  chronic 
interstitial  nephritis  is  only  an  analog  to  the  same  tolerance 
observed  in  all  cases  in  which  diabetes  is  associated  with  some 
other  severe  organic  disease  attended  with  cachexia  and  marasmus. 
Still,  I  have  seen  cases  in  which  the  cirrhotic  process  in  the  kidneys, 
though  developed,  has  left  a  fairly  good  general  state  of  health, 
and  in  which  this  increased  tolerance  has  been  perfectly  evident. 
Concerning  the  influence  of  the  kidneys  on  glycosuria,  reference  is 
made  for  further  particulars  to  what  is  said  in  chapter  iii  on  renal 
glycosuria. 

Diabetics  are  often  gouty,  and  gouty  patients  often  suffer  from 
renal  calculi,  which  are  not  rare  in  diabetes  of  the  mild  "lithemic  " 
type.  Budde  found  28  cases  of  nephrolithiasis  among  256 
diabetics. 

Otherwise,  diseases  of  the  urinary  organs  do  not  occur  much 
more  frequently  among  diabetic  patients  than  among  others. 
Schmitz,  who  sometimes  gathered  amazing  statistics,  quite  in- 
correctly mentions  cystitis  as  a  common  complication.  Senator, 
Fr.    Miiller,    Guiard,   and    others  have   seen    pneumaturia ;   Ernst, 


Il6  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Naunyn,  and  Hartge  have  found  microorganisms  (leptothrix,  sar- 
cina)  in  different  parts  of  the  urinary  tract.  Such  vegetations  easily 
occur  in  places  in  which  the  sweet  urine  comes  in  contact  with  the 
air,  but  the  germs  do  not,  as  a  rule,  spontaneously  ascend  the 
urethra,  and  complications  of  this  kind  are  comparatively  rare. 

The  kidneys  show  after  death  distinct  and  frequent,  but  not  con- 
stant and  not  marked,  changes.  With  the  naked  eye  generally 
some  enlargement  and  hyperemia  of  the  whole  organ  is  appreciable. 
On  section  the  cortex  often  presents  some  slight  fatty  and  opaque 
change  of  color ;  and  the  glomeruli  are  enlarged,  while  the 
medulla  is  distinctly  hyperemic.  Next  in  frequency  to  these  con- 
ditions the  kidney  is  found  without  distinct  changes.  Advanced 
parenchymatous  or  interstitial  alterations  are  exceptional.  The 
nephritis  of  diabetics  usually  represents  a  slight  development  of 
morbid  processes  both  in  the  interstitial  and  in  the  parenchymatous 
(epithelial)  tissue.  Sometimes  changes  like  those  of  the  large 
white  kidney  are  seen,  but  I  know  of  no  typical  case  of  this  kind. 

Under  the  microscope  some  degree  of  fatty  degeneration  may  be 
found,  especially  marked  in  the  convoluted  tubules,  but  only  rarely 
developed  to  such  a  degree  as  to  obliterate  the  nuclei  or  other- 
wise to  compromise  the  integrity  of  the  cells. 

Fichtner,  in  1888,  described  the  curious  appearance  of  a  trans- 
verse section  of  the  convoluted  tubules  showing  large  particles  of  fat, 
arranged  like  a  string  of  pearls,  in  the  degenerated  epithelial  cells 
along  the  basement  membrane.  Besides,  fatty  particles  are  found 
strewn  all  over  the  section  of  the  cells,  which,  however,  almost 
always  retain  their  structure. 

The  most  characteristic  (frequent,  but  not  constant)  microscopic 
change  is  represented  by  what  Armanni  *  designates  hyaline  meta- 
morphosis, Ebstein  hyaline  necrosis,  and  Straus  vitreous  degenera- 
tion.    I  believe  that  all  these  designations  denote  the  same  thing, 


*  Armanni  was  the  first  to  describe  this  curious  change,  which  he  considered  a  meta- 
morphosis of  leukocytes  that  had  entered  the  tubes  :  "  II  est  peu  probable  qu'il  s'agisse 
d'une  metamorphose  speciale  des  Elements  epitheliaux,"  he  says  in  the  French  edition  of 
Cantani's  work.  The  Germans  were  the  first  to  interpret  correctly  the  change  as  one  of  the 
epithelial  cells.  See  the  works  of  Frerichs,  Straus,  Marthen,  Albertoni  and  Pisenti, 
Trambusti  and  Nesbi,  Ferraro,  Obici,  Boccardi. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  11/ 

which  also  is  identical  with  what  Frerichs  and  Ehrlich  described  as 
enlarged,  polygonal,  hyaline,  epithelial  cells,  as  found  in  Henle's 
tubes.  Frerichs  and  Ehrlich  did  not,  however,  consider  the  change 
a  necrosis,  the  nuclei  in  their  cases  always  retaining  the  property  of 
taking  the  stains  distinctly.  They  laid  especial  stress  on  the  brown 
reaction  with  Lugol's  solution,  distinct  even  to  the  naked  eye, 
especially  in  the  limiting  zone,  in  the  section  of  the  kidney,  and  de- 
noting marked  infiltration  with  glycogen.  Later  investigations  leave 
scarcely  any  doubt  that  the  hyaline  metamorphosis  that  is  probably 
found  in  several  organs  besides  the  kidneys,  and  perhaps  even  apart 
from  diabetes,  is  an  independent  occurrence,  and  may  exist  without 
any  infiltration  with  glycogen,  which  substance,  however,  seems  to 
have  a  predilection  for  the  altered  cells  in  the  loops  of  Henle. 

Marthen  *  noted  that  van  Gieson's  stain  (hematoxylin  and  picric  acid)  col- 
ored the  hyaline  contents  of  the  enlarged  polygonal  cells  a  vivid  red.  Alber- 
toni  and  Pisenti  observed  hyaline  metamorphosis  in  dogs,  both  in  the  straight 
tubes  and  in  the  convoluted  tubules,  after  large  doses  of  acetone  (?)  ;  and  Tram- 
busti  and  Nesbi  noted  the  same  conditions  after  continued  large  doses  of 
phloridzin,  Pisenti  and  Acri,  according  to  my  opinion  without  sufficient  rea- 
son, distinguish  between  Armanni's  hyaline  metamorphosis,  which  they  con- 
sider identical  with  Frerichs'  and  Ehrlich's  cells  with  intact  nuclei  in  the  isth- 
mus of  Henle's  loops,  and  Ebstein's  hyaline  necrosis  in  the  convoluted  tubules, 
which  disintegrates  the  nuclei  of  the  cells. 

Boccardi  often  found  the  kidneys  normal  in  dogs  that  became 
diabetic  after  extirpation  of  the  pancreas,  but  sometimes  found  the 
vessels  and  the  tubules  dilated ;  the  interstitial  tissue  somewhat  in- 
creased, least  in  the  cortex,  most  in  the  limiting  zone  ;  Bowman's  cap- 
sules with  thickened  epithelium,  desquamation  of  the  endothelium, 
and  immigrated  white  blood-corpuscles  ;  glomeruli  either  enlarged 
or  atrophic  ;  epithelial  cells  in  a  state  of  fatty  degeneration,  which 
sometimes  went  so  far  as  to  disintegrate  ;  hyaline  degeneration  with- 
out any  glycogenic  infiltration  in  3  of  40  cases  ;  in  the  arteries 
the  adventitia  thickened  and  the  intima  exfoliated. 

The  sexual  organs  in  cases  of  diabetes  often  undergo  functional 
and  other  changes. 

Impotence  has  already  been  mentioned  among  the  nervous  symp- 

*"  Arch.  f.  path.  Anat.,"  1895. 


I  1 8  DIABETES    MELLITUS    AND    GLYCOSURIA. 

toms.  It  is  rarely  absolute,  apart  from  advanced  senility ;  but 
"  facultas  coeundi "  is  often  distinctly  weakened  from  the  moment 
the  glycosuric  dystrophy,  however  mild,  makes  its  appearance.  In 
rare  cases  sexual  vigor  remains  normal. 

Sterility  is  common  and  does  not  depend  on  "  impotentia  coeundi," 
as  it  exists  also  in  women.  The  cause  must  rather  be  looked  for 
in  some  influence  exerted  by  the  excess  of  sugar  or  by  toxins  in 
the  blood,  on  the  sperm  and  on  the  ova,  or  in  atrophy  of  the  testi- 
cles, or  the  ovaries,  or  in  the  diabetic  metritis  of  which  Lecorche 
speaks.  Still,  both  diabetic  men  and  women  may  produce  chil- 
dren, and  sometimes  conception  takes  place  even  in  the  severe 
stage.  Pregnancy  in  a  diabetic  woman  is  often  interrupted  by  mis- 
carriage in  the  fourth  or  fifth,  or  as  late  as  the  seventh,  month 
(Seegen,  Gaudard).  Further,  pregnancy,  which  sometimes  per  se 
causes  glycosuria  or  true  diabetes,  often  accelerates  the  progress  of 
an  existing  diabetes.  The  mortality  among  both  mothers  and  new- 
born children  is  very  great.  Of  the  latter,  41  in  every  100  die  soon 
after  birth  (Gaudard). 

I  have  seen  two  cases  of  diabetes  in  which  orchitis  appeared  as 
a  complication  without  obvious  cause. 

Those  parts  of  the  diabetic  patient's  skin  that  often  are  moist- 
ened by  the  sacchariferous  urine  readily  become  the  seat  of  vege- 
tation for  a  small  flora  of  low  fungi,  which  cause  eczema,  excori- 
ations, pruritus,  and,  especially  in  the  labia  majora,  sometimes  a 
series  of  furuncles.  Vulvitis  in  women,  balanitis,  balanoposthitis, 
and  sometimes  phimosis  in  men,  are  induced,  and  recur  readily  if 
not  restrained  by  the  use  of  antiseptic  lotions.  Both  in  men  and 
in  women  the  irritation  thus  caused  gives  rise  to  the  development 
of  papillomatous  excrescences,  which  are  known  to  have  changed 
into  epitheliomata  (Naunyn). 

Straynowski  mentions  atrophy  of  the  uterus  and  of  the  ovaries 
as  occurring  in  diabetic  women.  Analogous  changes  in  the  testicles 
may  be  quite  distinct  in  marantic  cases  in  men. 


Organs  of  Special  Sense. 

Diseases  of  the  eyes  are  extremely  common  in  diabetics,  and  there 
is  no  part  of  these  organs  that  has   not  been  named  as  the  seat  of 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  II9 

pathologic  processes  caused  by  the  glycosuric  dystrophy.  Though 
most  of  these  diseases  develop  only  after  the  diabetes  has  existed 
for  a  long  time,  they  not  rarely  constitute  the  primary  reason  for 
the  patient's  seeking  medical  aid,  and  they  thus  lead  to  the  dis- 
covery of  the  dystrophy.  It  has  been  said  that  two-thirds  of  all 
diabetic  patients  suffer  from  some  affection  of  the  eye.  This  esti- 
mate must  certainly  be  based  upon  hospital  statistics  and  upon 
observations  among  severe  cases,  as  in  private  practice,  with  its 
large  number  of  mild  cases,  the  proportion  is  much  smaller.  All 
the  deleterious  influences  already  named  as  belonging  to  the  gly- 
cosuric dystrophy  are  efficient  with  regard  to  the  eye,  but  the 
toxins  in  the  blood  in  many  cases  play  the  most  important  role ; 
and  some  of  the  diabetic  affections  of  the  eye  are  very  similar  to 
those  that  occur  during  long-continued  poisoning  with  alcohol  or 
tobacco,  or  to  those  that  may  be  produced  in  quite  a  short  time  by 
injections  into  the  blood  of  common  salt,  sugar,  naphthalin,  and 
other  substances. 

The  most  frequent  diabetic  affections  of  the  eye  are  cataract^ 
anomalies  of  accommodation  (especially  premature  presbyopicL),  retin- 
itis, and  inflammation  of  the  optic  nerve. 

Diabetic  amblyopia  or  amaurosis,  iritis  and  iridocyclitis,  opacities 
in  the  vitreous  body,  processes  in  the  cornea  and  sclera,  paralysis  of 
the  muscles,  and  some  other  dystrophic  troubles  are  less  common.* 

Diabetic  cataract  generally  develops  after  the  dystrophy  has  been 
present  for  many  years,  but  in  exceptional  cases  and  in  the  specific 
soft  form  it  may  appear  after  a  few  weeks  ;  this  happens  especially 
in  children.  The  affection  is  almost  always  bilateral,  and  is  found 
in  both  stages  of  diabetes,  although  it  is  more  frequent  in  severe 
cases,  without  bearing  any  fixed  relation  to  the  intensity  of  the 
diabetes. 

Weir  Mitchell  caused  cataract  in  frogs  by  subcutaneous  injections 

*  For  more  extensive  information  on  diabetic  affections  of  the  eye,  reference  may  be 
made  to  the  works  of  Leber,  Grsefe,  Foerster,  Jacobson,  Wiesinger,  Bouchard,  Schirmer, 
Knies,  Hirschberg,  Schmidt-Rimpler,  O.  Becker,  Deutschmann,  Berger,  Papanikolau, 
and  others.  The  essential  facts  can  be  found  in  the  "  Archiv  fiir  Ophthalmologie. "  The 
notes  of  my  own  cases  are  incomplete  with  regard  to  the  ocular  state,  as  I  always  refer 
the  patient  for  this  information  to  the  best  specialist  at  hand. 


I20  DIABETES    MELLITUS    AND    GLYCOSURIA. 

of  sugar ;  Richardson  noted  the  same  result  in  frogs  and  fishes  by- 
keeping  them  in  a  dilute  solution  of  sugar ;  and  cataracts  have 
since  been  induced  in  rabbits  and  frogs  by  introducing  sugar  into 
the  fold  of  the  conjunctiva.  Thus,  there  can  be  no  doubt  as  to 
the  efficiency  of  the  hyperglycemia  to  bring  about  cataract, 
whether  it  be  due  to  direct  irritation  of  the  tissues  of  the  lens  or 
to  their  desiccation.  The  cataracts  induced  artificially  begin  by 
the  formation  of  vacuoles  in  the  cells  ;  and  this  may  also  be  the 
case  with  diabetic  cataract  before  proliferation  and  disintegration 
of  the  cells  take  place.  The  diabetic  changes  in  the  vessels,  with 
local  nutritive  disturbances,  the  marasmus,  and  other  common 
influences,  may  contribute  to  the  result,  and  may  in  many  cases, 
especially  in  those  not  representing  the  typical  diabetic  soft  cataract, 
be  the  chief  etiologic  factors.  The  hypothesis  of  the  formation 
of  lactic  acid  in  the  aqueous  humor  of  the  eye  has  been  abandoned, 
since  investigations  have  proved  this  liquid  always  to  be  alkaline. 
In  the  liquids  of  the  eye,  in  the  lens,  and  in  the  vitreous  body, 
where  glucose  also  has  been  found  apart  from  diabetes,  this  sub- 
stance seems  to  be  increased  when  diabetes  develops  (Deutsch- 
mann,  Gorlitz,  Hedon  and  True). 

Typical  diabetic  cataract,  which  is  the  customary  variety  in 
young  persons  with  severe  diabetes,  is  of  the  soft  kind.  The 
process  begins,  according  to  Knies,  in  the  small  polygonal  cells  on 
the  posterior  aspect  of  the  anterior  part  of  the  capsule  of  the 
lens ;  the  adjacent  cellular  elements  of  the  lens  next  begin  to 
undergo  changes.  Becker  states  that  opacities  appear  at  first  in 
the  equatorial  zone,  then  in  the  posterior,  and  afterward  in  the 
anterior,  cortical  substance.  Whether  the  first  change  begins 
behind  or  in  front,  it  is  certain  that,  contrary  to  what  takes  place 
in  the  common  senile  cataract,  the  most  superficial  parts  of  the 
cortical  substance  are  the  first  to  undergo  change  in  the  develop- 
ment of  the  typical  diabetic  cataract.  The  first  macroscopic  mani- 
festation of  this  is  the  appearance  of  a  milky  layer  in  the  field  of 
the  pupil ;  then  the  whole  mass  of  the  lens  whitens,  and  mother-of- 
pearl-like  patches  become  visible  therein.  The  entire  development 
and  appearance  of  this  typical,  soft,  diabetic  cataract  strongly 
resemble  what  Bouchard  has  described  in  speaking  of  the  experi- 
mental cataract  caused  by  naphthalin. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  121 

The  soft  cataract  is,  however,  by  no  means  the  only  variety 
found  in  diabetic  patients,  and  so  far  as  my  experience  goes,  it  is 
not  even  the  most  frequent.  In  elderly  diabetics  one  often  finds 
the  usual  variety  of  senile  cataract,  with  central,  yellowish  sclerosis, 
and  bluish-gray,  radial  streaks  between  this  and  the  still  normal 
peripheral  parts  of  the  lens  and  (before  the  maturity  of  the  cataract) 
the  shadow  of  the  iris,  etc.  There  is  good  reason  to  believe  that 
these  changes  are  favored  by  the  glycosuric  dystrophy,  and  that 
they,  hke  diabetic  gangrene,  are  an  expression  at  the  same  time  of 
diabetes  and  of  senility. 

Konig  found  among  500  diabetic  patients  only  10  cases  of  cata- 
ract. Most  other  writers  made  the  proportion  higher.  I  have 
certainly  seen  more  than  10  cases  of  cataract  in  association  with 
diabetes,  though  I  have  not  yet  reached  500  cases  of  the  latter. 
This  may  be  due  partly  to  the  fact  that  several  cases  from  Dr. 
Nordenson's  extensive  clinical  material  have  been  referred  to  me  in 
Stockholm.  I  suppose  that  among  diabetic  patients  in  Carlsbad 
from  three  to  four  per  cent,  exhibit  cataractous  changes. 

Sometimes,  and  especially  in  severe  cases  of  diabetes,  one  finds' 
that  the  visual  near-point,  even  in  young  persons,  grows  more  and 
more  remote,  and  that  premature  p7'esbyopia  develops.  This  con- 
dition has  been  attributed  to  marasmus,  with  its  weakening  influ- 
ence on  the  muscles  of  accommodation,  to  alterations  in  the  vessels, 
to  neuritic  processes,  and  to  hemorrhages.  Diminished  elasticity 
of  the  lens  may  also  be  a  contributing  cause. 

Mydriasis  may  arise  from  toxic  influences.  In  the  presence  of  coma  the 
sphincter  of  the  pupil  may  be  seen  to  resist  and  to  react  in  quick  succession  to 
the  paralyzing  influence  of  the  poisons  in  the  system.  Still,  the  pupils  in  dia- 
betic persons  may  be  large  altogether  independently  of  diabetes— "  Cette  dilata- 
tion des  pupilles,  associee  le  plus  souvent  aux  symptomes  de  depression  est  un 
bon  signe  des  etats  neurastheniques,"  says  Bouveret  ("  La  Neurasthenie  "). 

Myopia  from  the  tumefaction  of  the  lens  is  the  most  frequent  anomaly  of 
accommodation  in  cases  of  diabetes,  if  it  develops  in  middle  age  or  later.  This 
fact  should  be  borne  in  mind,  and  the  urine  in  such  cases  of  myopia  should 
always  be  examined  for  glucose. 

Hypermetropia  is  mentioned  by  Horner  as  occurring  in  associa- 
tion with  diabetes. 
9 


122  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Diabetic  retinitis  (elaborately  described  by  Hirschberg)  belongs 
in  general  to  one  of  two  groups,  and  may  be  either  exudative  or 
hemorrhagic. 

Exudative  diabetic  retinitis — retinitis  diabetica  centralis  punctata — 
presents  small,  glossy,  nonpigmented  exudations  around  the 
central  portion  of  the  retina.  The  exudates  have  uneven  borders 
without  being  so  distinctly  stellate  as  the  exudates  of  albu- 
minuric retinitis  ;  here  and  there  a  small  point  of  blood  may  be 
visible.  There  is  no  discoloration  of  the  papilla ;  if  there  is,  a 
renal  complication  and  albuminuric  retinitis  should  be  suspected. 

Hemorrhagic  diabetic  retinitis  is  characterized  by  the  presence  of 
a  number  of  ecchymoses  of  varying  size  distributed  over  the  retina. 
They  sometimes  cause  amblyopia  and  occasion  quite  a  dubious 
prognosis,  as  they  often  represent  only  a  part  of  hemorrhages 
extended  over  different  regions  of  the  central  nervous  system.  I 
have  seen  them  attended  with  serious  symptoms,  sometimes  even 
with  perfect  loss  of  consciousness.  They  often  occur  successively 
over  some  length  of  time,  and  they  may  be  found  in  all  stages  in  the 
same  eye,  as  recent  hemorrhages  and  as  whitish  residual  patches. 
I  consider  these  small  retinal  hemorrhages  as  analogous  in  type  to 
the  small  hemorrhages  in  the  brain,  which  I  suspect  to  be  frequent 
in  inveterate  cases  of  diabetes,  and  which  often  may  be  unattended 
with  manifest  symptoms. 

Diabetic  optic  neuritis  is  so  much  like  the  neuritis  due  to  alcohol 
or  tobacco  that  its  diabetic  nature  has  been  called  in  question  even 
in  recent  times  {e.g.,  by  Mauthner).  Still,  Schmidt-Rimpler  found 
this  complication  in  34  among  140  cases,  and  Leber  in  14  among 
50  cases  of  diabetic  disorders  of  the  eye,  and  it  can  not  be  doubted 
that  inflammation  of  the  optic  nerve  is  not  uncommon  in  inveterate 
cases  of  diabetes  independently  of  both  alcohol  and  tobacco, 
though  it  often  escapes  detection.  When  developed,  it  presents  a 
central  scotoma,  with  deficient  color-perception,  corresponding  to 
the  macular  part  of  the  optic  nerve,  and  a  whitish  discoloration 
of  the  temporal  part  of  the  papilla.  The  differentiation  from 
neuritis  due  to  alcohol  or  tobacco  can  be  made  only  from  the  his- 
tory ;  in  some  cases  all  three  causes  may  contribute  to  the  result. 
Peripheral  contraction  of  the   field  of  vision   and   atrophy  and  dis- 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 23 

coloration  of  the  entire  papilla  may  ensue.  Diabetic  optic  neuritis, 
though  it  often  exhibits  temporary  improvement,  has  a  worse  prog- 
nosis than  the  analogous  affections  caused  by  alcohol  or  tobacco, 
which,  as  is  well  known,  are  themselves  quite  obstinate,  even  after 
the  removal  of  their  causes. 

Amblyopia  and  amaurosis  may  arise  in  the  course  of  diabetes 
from  such  alterations  within  or  without  the  eye  as  ordinarily  give 
rise  to  them,  but  they  may  also  result  from  the  action  of  diabetic 
toxins  (Leber).  In  the  latter  event  the  danger  of  corna  is  never  to 
be  lost  sight  of.  In  the  last  case  of  this  kind  that  I  have  treated 
exceedingly  elaborate  investigation  by  Dr.  Nordenson  failed  to  dis- 
close any  other  than  a  toxic  cause  ;  the  deflection  of  the  ray  of 
polarized  light  to  the  left,  due  to  /5-oxybutyric  acid  in  the  urine, 
equaled  a  little  more  than  0.5  degree  with  Hoppe-Seyler's  instru- 
ment.    The  patient  died  about  two  months  afterward  in  coma. 

Diabetic  iritis  *  is  a  torpid,  suppurative  process  without  ulceration 
of  the  cornea ;  it  usually  appears  in  both  eyes,  and  is  observed  in 
advanced  cases.  Leber  noted  hypopyon  in  two  among  nine  cases. 
A  fibrinous  deposit  over  the  whole  pupil  was  present  in  several 
cases,  but  disappeared  quickly  and  completely  under  the  influence 
of  sodium  salicylate.  In  some  cases  only  an  adhesive  iritis  is 
found,  with  synechiae.  Finally,  there  seems  to  exist  exceedingly 
torpid  forms  of  the  disease,  which  develop  almost  imperceptibly 
until  they  cause  a  change  in  the  color  of  the  iris.  The  whole  pro- 
cess may  lead  to  atrophy  of  the  iris,  sometimes  to  glaucoma. 

The  choroid  may  participate  in  the  process  and  cause  opaci- 
ties in  the  vitreous  body.  Leber  observed  detachment  of  the 
choroid. 

Hemorrhages  and  opacities  in  the  vitreous  body  have  their  origin 
in  the  retina  or  in  the  choroid. 

Diabetic  keratitis  presents  itself  as  a  parenchymatous  inflammation 
of  neuroparalytic  character,  and  may  lead  to  ulceration  and 
suppuration. 

*  Leber,  "  Arch.  f.  Ophthal.,"  1885. 


124  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Scleritis  and  episcleritis  are  also  mentioned,  but  their  relation  to  diabetes 
seems  undecided. 

The  eyelids  may  become  the  seat  of  Jiordeobnn,  cJialazion, 
eczema,  or  herpes.  HeviorrJiages  in  the  conjunctiva  are  considered 
to  be  an  effect  of  diabetes  and  a  special  reason  for  analysis  of  the 
urine. 

The  intracranial  hemorrhages  that  are  likely  to  complicate  dia- 
betes of  long  standing  sometimes  cause  paralysis  of  the  muscles  of 
the  eye,  and  any  one  that  has  seen  a  large  number  of  diabetic 
patients  must  also  have  seen  such  disturbances  of  function  on  the 
part  of  the  abducens,  the  oculomotor,  the  trochlear,  or  the  facial 
nerve,  with  strabismus,  lagophthalmos,  ptosis,  etc.  In  some  cases 
rapid  absorption  and  complete  restitution  take  place.  I  have  also 
seen  paretic  symptoms  remain  for  several  years  and  for  the  re- 
mainder of  the  patient's  life. 

Being  constantly  on  the  alert  for  the  many  severe  diseases  of  the 
eye  that  threaten  the  diabetic  patient,  one  is  likely  to  overlook 
symptoms  of  a  purely  neurotic  and  less  dangerous  nature.  If,  how- 
ever, the  physician  makes  it  his  custom  to  ask  concerning  such 
symptoms,  and  sometimes  even  if  he  does  not,  he  will  gain  infor- 
mation indicating  the  frequency,  also  in  this  field,  of  neurasthenic 
symptoms  in  cases  of  diabetes.  The  practitioner  who  is  not  well 
versed  in  the  use  of  the  ophthalmoscope  will  often  find  difficulty 
in  excluding  organic  disease.  Sometimes  neurasthenic  asthenopia, 
with  local  subjective  sensations  and  deficiency  of  endurance  in  the 
use  of  the  eyes,  is  observed.  Many  diabetics  display  marked  hyper- 
esthesia for  light. 

Diseases  of  the  ears'^  are  much  rarer  complications  of  diabetes  than 
diseases  of  the  eyes.  Central  disturbances  of  the  acoustic  nerve, 
whose  center  is  quite  near  to  the  situation  of  Bernard's  puncture, 
are  exceedingly  rare. 

Otitis  follicularis  externa,   or  furuncle   of  the  external  auditory 

*See  Kuhn,  "  Archiv  f.  Ohrenkr.,"  Bd.  xix  ;  Kirchner,  "  Deutsche  med.  Wochen- 
schr.,"  1887  ;  Korner  and  v.  Wildt,  "  Zeitschr.  f.  Ohrenheilk.,"  Bd.  xxiii. 


SYMPTOMS   AND  COMPLICATIONS  OF   DIABETES.  125  . 

canal,  is  undoubtedly  more  common  in  diabetics  than  in  other  indi- 
viduals. 

Otitis  media  diabetica  sometimes  leads  to  suppuration  of  the 
internal  ear  and  its  osseous  parts,  and  one  now  and  then  sees 
patients  with  scars  after  operations  in  the  mastoid  region.  Inflam- 
mation of  the  middle  and  internal  parts  of  the  ear  may  cause 
meningitis,  but  few  such  cases  are  recorded  ;  and  these  processes  in 
the  ear,  which  owe  their  origin  to  bacteria  (streptococcus,  staphylo- 
coccus, etc.),  scarcely  occur  in  more  than  one  per  cent,  of  all  cases 
of  diabetes. 

I  have  had  under  observation  a  rare  and  interesting  case  of  trauma  of  the 
inner  ear  in  a  case  of  diabetes.  Mr. ,  a  Scandinavian  merchant,  sixty- 
six  years  old,  had  suffered  from  diabetes  for  about  eighteen  years.  He  was  in 
the  mild  stage  of  the  dystrophy,  and  the  glycosuria  disappeared  when  the  car- 
bohydrates were  restricted  to  about  thirty-five  grams.  I  was  called  early  one 
morning  to  the  patient,  who  had  fallen  out  of  bed  during  the  night,  and  somehow 
had  been  struck  on  the  left  side  of  the  head  by  a  basin  filled  with  water  that 
had  fallen  over  him.  The  left  tympanic  membrane  had  ruptured  and  the 
pillow  was  stained  with  serous  liquid  slightly  mixed  with  blood.  The  pulse 
was  at  least  normal  in  frequency,  and  thus  indicated  no  irritation  of  the  pneu- 
mogastric  nerve.  There  were  no  symptoms  referable  to  the  eyes,  but  the 
patient  presented  a  cotnplete  inability  to  maintain  equilibriutn.  I  supposed  a 
fissure  through  the  labyrinth  and  the  semicircular  ducts  had  taken  place. 
During  proper  local  and  general  treatment  the  patient  otherwise  recovered  in 
the  course  of  some  weeks,  but  the  inability  to  maintain  equilibrium,  subsiding 
very  slowly,  remained  for  several  months. 

Ordinary  functional  nervous  troubles  of  auditory  character  are 
not  absent.  The  diabetic  patient  often  exhibits  a  marked  acoustic 
hyperesthesia,  which  sometimes  causes  him  to  make  elaborate  ar- 
rangements to  avoid  noise.  Subjective  acoustic  perceptions,  espe- 
cially during  the  night  (tinnitus  aurium,  etc.),  are  not  rare.  Otalgia 
is  sometimes  complained  of  The  cause  may  then  be  looked  for  in 
the  teeth,  which  are  so  commonly  carious  in  diabetes.  In  other 
cases  the  otalgia  is  only  a  secondary  manifestation  of  an  extensive 
neuralgia  in  the  distribution  of  the  fifth  pair  of  nerves  (auriculo- 
temporal branch),  or  of  neuralgia  in  the  distribution  of  the  occipital 
'or  the  auricularis  magnus  nerve.  The  differentiation  must  then  be 
made  between  a  merely  nervous  and  a  rheumatic  affection.  Rheu- 
matic infiltrations  in  the  soft  parts  of  the  head,  which  constitute  one 


126  DIABETES    MELLITUS    AND    GLYCOSURIA. 

of  the  most  attractive  hobbies  of  the  professional  masseur,  may  be 
the  cause.  Sometimes  pruritus  or  hyperesthesia  or  paresthesia  of 
the  outer  ear  is  spoken  of 

The  skin  often  presents  local  or  general  changes. 

General  changes  are  observed  in  the  severe  stage  or  in  advanced 
cases  in  the  mild  stage.  I  have  already  mentioned  the  diminished 
secretion  of  the  sebaceous  and  the  sudoriferous  glands — the  astea- 
tosis  and  the  anhidrosis — and  the  resulting  marked  dryness  of  the 
skin.  The  cause  of  this  condition  resides  not  only  in  the  more 
tenacious  retention  of  the  water  of  the  blood  within  the  vessels  by 
reason  of  the  hyperglycemia,  but  also  in  the  atrophy  of  the  skin,  not 
rarely  found  in  the  severe  stage,  especially  on  the  hands,  and  still 
more  often  in  the  face,  where  one  observes  the  change  that,  in  its 
fully  developed  state,  is  called  "  glossy  skin."  The  skin  is  mani- 
festly thin,  and  there  is  a  marked,  circumscribed,  cyanotic  redness 
of  the  cheeks. 

It  is  in  such  cases  that  diabetic  pruritus  is  best  marked.  It  is 
usually  much  less  intense  than  in  cases  of  icterus,  for  instance,  and 
it  rarely  constitutes  a  serious  annoyance. 

I  have  already  mentioned  the  furuncle,  the  carbuncle,  the  "  mal 
perforant"  and  Raynaud's  disease,  the  different  forms  of  diabetic 
gangrene  and  the  different  forms  of  eczema,  and  other  changes  that 
result  when  the  skin  is  often  moistened  by  the  urine.  It  is  chiefly 
these  latter  eruptions  that  the  French  call  "  diabetides,"  which 
appellation  should  not  suggest  an  idea  of  anything  pathognomonic. 

So  far  as  I  know,  there  is  not  a  single  change  in  the  skin  in 
diabetes  that  may  not  occur  apart  from  this  dystrophy.  This  is 
true  even  of  the  rare  "  xanthoma  tuberosum  diabeticum,"  observed 
hitherto,  in  all,  in  about  thirty  cases.  The  one  case  that  I  have 
seen  presented  the  customary  solid,  yellowish-red  excrescences,  as 
large  as  peas,  distributed  in  considerable  numbers  chiefly  on  the 
extremities.  They  were  most  numerous  over  the  triceps  muscle  on 
the  upper  part  of  the  arms  and  over  the  extensors  on  the  lower 
part.  A  few  were  to  be  seen  on  the  flexor  aspect.  On  the  legs 
they  were  exceedingly  numerous  over  the  quadriceps  femoris, 
especially  in  the  vicinity  of  the  knee-joint.  A  few  were  to  be 
seen  on  the  outer  sides  of  the  calves  and  on  the  dorsal  aspect  of  the 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  12/ 

tibiotarsal  joint.  There  were  a  few  on  the  shoulders  and  on  the 
neck,  and  one  in  the  left  external  auditory  canal.  Neither  in 
their  distribution  *  nor  in  any  other  feature  could  I  discover  any 
difference  from  what  I  have  seen  of  "  xanthoma  tuberosum  " 
attending  icterus.  The  patient  was  a  man  twenty-eight  years  old, 
suffering  from  severe  diabetes,  without  icterus. 

The  formations  that  Kaposi  calls  "  dermatitis  papulosa  diabetica^  with  ex- 
crescences in  patches  on  an  inflamed  base,  may  probably  also  be  seen  inde- 
pendently of  diabetes,  in  association  with  which  they  are  extremely  rare. 

Besides  the  skin-diseases  already  mentioned,  diabetic  patients 
frequently  yield  the  dermatologist  varied  clinical  material.  I  have 
seen  erythema,  urticaria,  lichen,  acne,  impetigo,  rupia,  herpes  (in- 
cluding herpes  zoster^,  pemphigus,  pityriasis,  ichthyosis,  psoriasis,  all 
sorts  of  eczema,  petechice.  Purpura  hemorrhagica  (Dujardin-Beau- 
metz)  and  pityriasis  rubra  (Harden)  have  been  mentioned.  For 
some  of  these  affections  we  may  look  to  the  marasmus  as  the  chief 
cause.  In  other  cases  the  hyperglycemia  may  be  efficient.  In  a 
great  many  instances  the  connection  with  diabetes  may  consist  only 
in  the  angioneurotic  constitution  common  in  diabetic  patients,  who, 
in  fact,  often  mention  that  they  suffered  from  their  cutaneous 
troubles  long  before  glycosuria  arose. 

The  hair  of  diabetic  patients  offers  two  peculiarities  :  in  conse- 
quence of  the  asteatosis  and  anhidrosis  it  is  often  dry,  and  therefore 
presents  a  ragged  appearance;  and  it  is"  often  prematurely  gray,  f 
Diabetes  may  have  some  influence  in  causing  baldness,  and  "  de- 
fluvium  capillorum "  is  mentioned  by  more  than  one  writer  on 
this  subject.   Marked  effects  of  this  kind  are  not  conspicuous,  and  I 

*  The  distinction  between  diabetic  and  icteric  xanthoma  is  said  to  be  that  the  former 
is  equally  spread  over  the  whole  body,  while  the  latter  is  distributed  as  in  my  diabetic 
patient.     Kaposi  does  not  acknowledge  the  existence  of  a  specific  diabetic  xanthoma. 

t  Susruta,  about  1200  years  ago,  mentioned  a  peculiar,  wild  appearance  of  the  diabetic 
patient's  hair.  I  suppose  that  the  gray  hair  has  no  direct  connection  with  diabetes,  but 
depends  on  the  great  emotional  sensitiveness  common  among  diabetic  patients.  The 
curious  and  sometimes  remarkably  sudden  influence  depressing  emotions  have  in  this 
respect  is  well  known.  Thus,  it  is  related  that  a  Hindu  suddenly  turned  gray  just 
before  his  execution  during  the  great  mutiny  ("  Ind.  Med.  Times  and  Gazette,"  1859) ; 
as  did  also  Ludovico  Sforza  when  he  was  taken  prisoner,  and  Guarini  da  Verona  when 
he  lost  his  Greek  manuscripts.  (See  H.  C.  Wood,  "Nervous  Diseases,"  Philadelphia, 
1887.) 


128  DIABETES    MELLITUS    AND    GLYCOSURIA. 

know  many  patients  who,  after  long  years  of  abundant  glycosuria, 
still  keep  a  luxuriant  growth  of  hair  on  their  heads. 

The  nails  sometimes  show  distinct  alterations.  Paronychia  is  not 
rare  and  sometimes  causes  the  nails  to  fall  out.  In  other  cases  the 
nails  change  without  any  cause  whatever  discoverable  to  the  naked 
eye.  They  become  thick,  brittle,  discolored  and  brownish,  markedly 
curved  in  both  directions,  and  may  then  fall  out.  It  seems  to 
me  that  this  occurs  chiefly  in  inveterate  cases  complicated  with 
gout,  and  in  cases  with  distinct  neuritis.  It  is  certain  that  such 
changes  are  not  related  to  the  intensity  of  the  diabetes,  and  one 
often  finds  the  nails  on  the  hands  and  feet  perfect  in  patients  toward 
the  close  of  life  after  years  of  the  dystrophy  in  its  severe  stage. 


Organs  of  Locomotion. 

The  patient  in  the  mild  stage  of  diabetes  is  generally  an  indolent 
person,  of  sedentary  habits,  to  whom  the  physician  must  preach 
long  sermons  as  to  the  utility  and  the  necessity  of  bodily  exercise, 
and  whose  muscular  strength  and  endurance  usually  are  much 
smaller  than  seems  indicated  by  his  often  robust  appearance.  The 
diabetic  patient  in  the  severe  stage  often  drags  himself  along  with 
an  unsteady  gait,  and  is  made  excessively  tired  by  exercise  that  con- 
stitutes a  daily  salutary  habit  in  healthy  persons,  but  which  in  some 
cases  of  diabetes  may  be  sufficient  to  cause  coma.  A  patient  of 
this  kind  will  rise  late  and  go  early  to  bed,  and  his  lassitude,  his 
feeling  of  excessive  muscular  weakness,  will  sometimes  even  keep 
him  in  bed  throughout  the  twenty-four  hours. 

The  muscular  neurasthenia  is  partly  the  cause  of  the  diabetic's 
constant  feeling  of  tiredness.  The  dryness  of  the  muscular  tissues 
— much  dwelt  upon  by  Dieulafoi — probably  is  an  important  causa- 
tive factor  in  cases  of  marked  hyperglycemia.  The  excessive 
amount  of  sugar  in  the  blood  in  a  similar  manner  also  directly 
affects  the  motor  nerves.  In  marantic  cases  the  vmscles  often  are 
extremely  atrophic  and  reduced  to  ribbon-like  proportions,  of 
which  no  great  mechanical  effects  can  be  expected. 

The  bones  in  cases  of  severe  diabetes  have  been  found  remarkably 
light  and  porous,  and  fractures  often  heal  slowly  and  imperfectly. 
The  enormous  amount  of  those  salts  that  enter  into  the  constitution 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 29 

of  the  bones  sometimes  found  in  severe  cases  (v.  Ackeren,  Fodor)  in 
the  urine  seems  also  to  denote  disintegration  in  those  structures.  So 
far  as  I  know,  there  have  been  no  systematic  investigations  of  these 
processes  and  of  the  consequent  osteoporosis  in  diabetes.  Charrin 
and  Guignard,  with  many  others,  accept  the  existence  of  this  dia- 
betic osteoporosis  and  believe  it  due  to  the  acidosis.  Considering 
that  the  acids  only  diminish,  but  never  entirely  neutralize,  the  alka- 
linity of  the  blood,  I  am  more  inclined  to  believe  in  a  general  mar- 
antic or  in  a  purely  trophic  influence,  analogous  to  that  observed 
by  Kassowitz  in  the  bones  of  rabbits'  legs  after  section  of  the  sciatic 
nerve. 

As  there  are  to  be  found  all  stages  between  a  normal  power  of 
assimilating  carbohydrates  and  the  greatest  possible  reduction  of 
that  power,  so  also,  with  regard  to  the  general  clinical  picture,  there 
are  all  possible  intermediate  gradations  between  the  healthy  indi- 
vidual and  the  patient  approaching  diabetic  coma.  There  are, 
especially,  many  persons  who  live  on  the  border-land  between  what 
may  still  appropriately  be  called  the  mild  and  the  severe  stage, 
and  there  may  be  only  a  slight  clinical  difference  between  a  patient 
who  is  free  from  glycosuria  during  abstinence  from  carbohydrates 
and  one  who  even  under  such  dietetic  conditions  excretes  a  few 
grams  of  glucose  in  the  course  of  the  twenty -four  hours.  If,  however, 
a  patient  is  selected  from  the  middle  of  each  of  the  two  stages,  quite 
marked  clinical  differences  will  generally  be  found  between  these 
two  representatives  of  the  glycosuric  dystrophy. 

The  history  often  presents  remarkable  points  of  difference.  Mild 
diabetes  is  often  discovered  by  mere  accident ;  e.g.,  on  examination 
for  life-insurance.  In  other  cases  neurasthenic  symptoms,  or  some 
local  trouble,  or  some  slight  signs  of  dystrophy  guide  the  sus- 
picions of  the  physician  in  the  right  direction.  The  diabetic 
symptoms,  if  there  are  any  at  all  apart  from  the  glycosuria,  have 
developed  gradually,  and  the  dystrophy  has  only  slightly  affected  the 
patient,  who  often  is  unable  to  give  any  definite  information  as  to  the 
time  of  the  beginning  of  the  diabetes.  Severe  diabetes — often  in  a 
short  while — changes  a  state  of  health  into  one  of  marked  ill-health, 
and  the  patient  is  often  able  to  name  at  least  the  month,  and  some- 
times the  day,  of  appearance  of  the  first  symptoms.      Even  in  such 


130  DIABETES    MELLITUS    AND    GLYCOSURIA. 

cases,  in  which  at  first  restriction  of  carbohydrates  suppresses  the 
glycosuria,  sudden  appearance  of  diabetic  symptoms  is  an  unfavor- 
able sign,  and  makes  probable  the  future  development  of  the  severe 
stage  of  the  disease. 

The  actual  state  of  the  representatives  of  the  two  classes  men- 
tioned usually  presents  a  number  of  salient  points  of  difference. 
The  patient  with  mild  diabetes  may,  even  after  years,  appear  as  a 
man  of  quite  fair,  sometimes  even  of  florid,  health,  with  a  normal 
complexion,  a  robust  form,  and  active  habits.  He  is  sometimes 
troubled  with  adiposity  or  with  gout,  almost  always  with  "  ner- 
vousness." He  may,  however,  perform  quite  important  duties  in  a 
private  or  a  public  capacity,  and  can  easily  conceal  his  diabetes, 
with  its  insignificant  and  vague  symptoms,  from  the  world.  The 
severely  affected  patient,  with  acid  toxins  in  the  blood, — the  "  acid- 
osis,"— often  manifestly  presents  evidence  of  that  marasmus  which 
constitutes  the  most  essential  distinction  between  severe  and  mild 
cases.  He  is  generally  thin,  often  extremely  so  ;  his  movements 
are  weak  ;  his  gait  uncertain  ;  the  expression  of  his  face  either  lan- 
guid and  drowsy  or  uneasy,  sometimes  desperate  ;  the  complexion 
either  of  a  cachectic  pallor  or  marked  by  an  unhealthy  cyanotic  red- 
ness of  the  cheeks.  His  mere  aspect  reveals  his  serious  state,  and 
his  family  and  friends,  even  without  recognizing  the  nature  of  his 
disease,  often  realize  that  his  days  are  numbered. 

Then,  the  issue  in  the  two  stages  of  glycosuric  dystrophy  is  dif- 
ferent. Mild  diabetes  is  in  no  specific  way  fatal  ;  if  it  does  not 
develop  into  a  severe  diabetes,  the  patient  will  live  until  stricken 
by  some  accidental  intercurrent  or  complicating  affection,  which, 
though  perhaps  less  frequently,  may  occur  apart  from  diabetes, 
such  as  acute  pneumonia,  carbuncle,  cerebral  hemorrhage,  heart- 
failure,  etc.  Severe  diabetes,  however,  leads  to  death  in  most 
cases  through  a  specific  complication  caused  by  the  presence  of 
toxins  in  the  blood.  Acetone  may  exert  some  slight  contributory 
influence  ;  the  diacetic  acid  and  the  low  fatty  acids,  by  reason  of 
their  small  amounts,  can  not  per  se  bring  about  the  result.  The 
/9-oxybutyric  acid,  which  may  be  formed  in  large  quantities,  is  the 
chief  factor  in  the  production  of  the  acid  diathesis,  the  "acidosis," 
and  of  the  final  acute  poisoning,  which,  when  once  begun,  gener- 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  I3I 

ally  in  a  short  time  leads  to  paralysis  of  the  nervous  centers,  and  is 
known  as — 


Diabetic  Coma.* 

The  development  of  diabetic  coma  may  be  excited  by  some  in- 
considerable depressing  incident,  such  as  emotion,  fatigue,  or  a 
slight  indisposition.  A  common  cause,  or,  perhaps  better,  a  com- 
mon forerunner,  of  coma  is  obstinate  constipation,  which,  after  coma 
has  set  in,  may  give  way  to  profuse  fetid  diarrhea.  Coma  is,  how- 
ever, promoted  not  only  by  all  depressing  influences,  but  by  any 
cause  that  increases  the  acid  diathesis,  the  acidosis.  Every  agency 
that  has  both  these  effects  is  especially  dangerous,  and  I  believe 
that  the  most  frequent  immediate  cause  of  coma  arises  from  a  too 
rigid  restriction  of  carbohydrates,  with  consequent  inanition  and  in- 
crease of  diacetic  acid  and  of  /?-oxybutyric  acid  in  the  blood. 

A  feeling  of  extreme  weakness,  of  drowsiness,  and  of  headache 
generally  precedes  the  attack.  Sometimes  there  is  complete  loss 
of  appetite.  Severe  epigastric  pains,  sometimes  accompanied  by 
vomiting,  are  not  rare,  and  may  continue  for  some  time  before  the 
paralytic  stage  develops. 

The  first  manifest,  and  the  most  characteristic,  symptom  of  coma 
is  a  sudden  dyspneic  frequency  and  depth  of  respiration  ;  at  the 
same  time  the  frequency  of  the  pulse  increases.  Respiration  fol- 
lows no  distinct  type, — especially  not  the  Cheyne-Stokes, — inspira- 
tion taking  place  forcibly  and  deeply  twenty  or  thirty  times  a 
minute  in  a  blowing  manner,  even  in  cases  in  which  postmortem 
examination  subsequently  shows  a  normal  state  of  the  lungs.  The 
pulse  runs  up  to  from  1 30  to  i  50  or  more,  becomes  extremely  small, 
and  can  soon  be  no  longer  counted.  The  pupils  may  be  strongly  con- 
tracted. Mental  excitation,  often  of  great  terror,  may  precede  the 
depressing  symptoms.     Sometimes  the  dyspneic  respiration  and  the 

*  Diabetic  coma  was  first  described,  in  1854,  by  v.  Dusch,  but  it  was  little  known  in  the 
profession  until  described  twenty-one  years  later  by  Kussmaul.  The  majority  of  my 
diabetic  patients  in  the  severe  stage  have  died  in  coma.  Frerichs,  among  250  patients, 
diabetic  at  the  time  of  their  death,  found  150  cases  of  coma.  A.  James,  of  Edinburgh, 
however,  encountered  only  24  instances  of  coma  among  50  fatal  diabetic  cases.  In  the 
other  26  cases  death  was  due  to  pulmonary  tuberculosis  in  16  and  to  acute  pneumonia  or 
gangrene  of  the  lungs  in  8  cases. 


132  DIABETES    MELLITUS    AND    GLYCOSURIA. 

quick,  small  pulse  may  continue  for  many  hours,  or  even  for  days, 
before  paralytic  symptoms  set  in.  Sometimes  the  first  stage  of  ex- 
citation may  pass  so  quickly  and  be  so  little  marked,  and  the  par- 
alytic stage  set  in  so  suddenly,  that  the  condition  can  hardly  be  dis- 
tinguished from  apoplexy  or  primary  paralysis  of  the  heart.  Sooner 
or  later  the  sensorium  becomes  clouded  ;  but  even  before  this  is 
manifest,  the  speech  may  denote  incipient  motor  disturbance.  The 
depression  is  generally  supreme,  signs  of  excitation  being  only 
slight  and  of  short  duration,  and  spasm  being  sometimes  scarcely 
perceptible.  The  extremities  become  icy  cold  ;  the  temperature, 
which  often  before  the  attack  was  below  the  normal,  now  sinks  still 
further.  During  this  period  the  glucose,  the  urea,  the  toxic  acids, 
and  the  other  products  of  metabolism  in  the  urine  may  be  dimin- 
ished.* I  may  refer  also  to  the  small  casts  from  the  kidneys  that 
Kiilz,  among  others,  found  to  be  numerous  and  constant  (?)  during 
coma.  The  comatose  state  may  last  for  days,  rarely  for  weeks, 
and  sometimes  only  for  hours.  The  average  duration  of  life  after 
the  first  manifest  symptoms  have  appeared  may  be  estimated  at  two 
or  three  days.  Even  if  the  patient,  as  sometimes  happens,  almost 
completely  regains  consciousness,  and  all  symptoms  of  comatose 
depression  recede,  restitution  to  the  preexisting  state — though  it  is 
mentioned  in  literature  by  trustworthy  observers — is  extremely  rare. 
When  the  nervous  centers  have  once  been  attacked,  all  treatment, 
however  energetic  and  quickly  applied,  almost  always  fails  to  bring 
about  permanent  recovery,  and  the  physician  does  well  not  to  let 
transitory  improvement  deceive  him  as  to  the  approaching  fatal 
issue.  The  last  hours  are  generally  quiet,  with  scarcely  any  other 
signs  of  life  than  the  respiration  and  the  pulse,  and  dilatation  and 
contraction  of  the  pupils,  the  latter  often  asynchronous. 

Diabetic  coma  is  a  state  of  poisoning — there  is  no  doubt  about  that  in  the 
mind  of  any  physician  who  has  once  seen  it ;  but  opinions  as  to  the  kind  of 
poison  differ  greatly.  At  one  time  the  hyperglycemia  was  suspected  as  a 
cause,  but  I  consider  this  view  to  have  only  historic  interest.  The  increased 
amount  of  sugar  in  the  blood  may  reach  higher  figures  in  mild  cases  of  diabetes 
with  a  free  diet  than  in  severe  cases  with  restriction  of  the  carbohydrates ;  but 
mild  cases  of  diabetes — i.  e.,  cases  in  which  glycosuria  disappears  when  caibo- 

*  Munzer  and  Strasser,  however,  have  found  the  nitrogen  in  the  urine  increased  dur- 
ing coma  ;  the  excess  may,  however,  have  been  produced  before. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 33 

hydrates  are  excluded — do  not  develop  coma.  I  consider  that  all  reports  of 
such  an  occurrence  are  the  result  of  mistake,  and  represent  cases  of  uremia  or 
of  primary  heart-failure,  etc.  Complete  exclusion  of  carbohydrates  causes 
diminution  in  the  hyperglycemia,  but  notoriously  increases  (the  acidosis  and) 
the  danger  of  coma.  Diabetic  coma  is  sometimes  not  unlike  uremia,  from 
which  it  differs  in  several  respects,  and  especially  in  the  marked  dyspneic 
respiration,  though  this  may  to  some  extent  be  present  in  the  final  stages  of  a 
number  of  different  diseases.  Besides,  patients  die  in  diabetic  coma  in  the 
absence  of  serious  changes  in  the  kidneys.  The  Scotch  theory  as  to  fat- 
embolism  in  the  brain  has  scarcely  any  basis  at  all,  and  has  not  survived. 
From  1857,  when  Fetters,  in  a  case  of  coma,  found  acetone  in  the  blood  and 
in  the  urine,  the  theory  of  acetonemia  as  the  cause  of  diabetic  coma  was 
widely  accepted ;  but  Kussmaul  refutes  this  theory,  and  Frerichs,  in  the 
seventies,  Albertoni,  in  1884,  and  others  proved  that  the  toxicity  of  acetone, 
especially  in  view  of  the  small  quantity  produced  in  diabetes,  is  insufficient  to 
be  considered  a  cause  of  death.  Fere,  in  fact,  does  not  consider  acetone  much 
more  poisonous  than  ethylic  alcohol,  which  is  drunk  in  such  quantities  by 
millions  of  human  beings. 

Gerhardt,  in  1865,  discovered  his  most  important  reaction  ;  and  when  Deich- 
miiller,  Tollens,  and  v.  Jaksch  had  found  it  to  be  due  to  diacetic  acid,  suspicion 
fell  on  this  substance;  but  here,  again,  the  toxicity  and  the  quantity  were  too 
small.  When  acetone  and  diacetic  acid  both  pass  over  during  distillation  as 
acetone,  scarcely  ten  grams  of  the  latter  can  be  obtained  from  the  daily 
urine ;  and  Brieger  showed  that  injection  into  the  blood  of  twenty  grams  of 
diacetic  acid  left  the  nervous  system  perfectly  intact. 

Hallervorden  had  found  the  quantity  of  ammonia  excreted  in  severe  cases  of 
diabetes  enormously  increased,  and  he  and  Coranda  found  that  this  increased 
ammonia  corresponded  to  an  increased  excretion  of  acid.  Walther,  in  1877, 
showed  that  injection  of  acids  into  dogs  produced  a  state  quite  similar  to 
diabetic  coma.  On  this  basis  Stadelmann,  in  1883,  made  further  investigations 
in  cases  of  severe  diabetes,  and  found  what  he  first  considered  as  a-crotonic 
acid,  but  what  Minkowski  and  Kiilz  later  proved  to  be  /3-oxybutyric  acid. 
Since  Kiilz  afterward  found  that  the  excretion  of  /?-oxybutyric  acid  may  amount 
to  more  than  200  (226.5)  grams  in  twenty-four  hours,  this  acid,  not  with- 
out good  reason,  has  been  considered  to  be  the  principal  cause  of  diabetic 
coma,  though  the  other  acids  (diacetic  acid  and  fatty  acids  of  low  order),  the 
acetone,  and  perhaps  other  still  unknown  toxins*  may  exercise  a  contributory 
influence. 

In  this  book  I  have  adhered  to  the  old  division  of  diabetes  into 
a  mild  and  a  severe  stage,  and  this  I  beheve  to  be  the  best  and 
most  practical,  founded,  as  it  is,  on  the  absence  or  presence  of  gly- 
cosuria with  abstinence  from   carbohydrates.      Of  late,   however. 


*  Ammonia  may  be  present  in  increased  quantity  through  the  influences  of  other  acids 
than  /3-oxybutyric  acid  (Rumpf,  Strasser,  and  Miinzer). 


134  DIABETES    MELLITUS    AND    GLYCOSURIA. 

another  classification  has  been  made,  namely,  pancreatic,  neurogenic, 
and  constitutional  diabetes. 

The  pancreatic  and  the  neurogenic  varieties  are  considered,  as  a 
rule,  to  form  together  what  I  have  called  severe  diabetes,  character- 
ized by  its  sudden,  comparatively  acute  appearance,  its  rapid  de- 
velopment, the  autophagy,  the  acidosis,  and  the  frequency  of  death 
in  diabetic  coma.  Pancreatic  diabetes  is  distinguished  from  neuro- 
genic diabetes  by  (i)  the  absence  of  a  nervous,  etiologic  factor  ;  (2) 
the  presence  of  local  symptoms  referable  to  the  pancreas  ;  (3)  pecu- 
liar qualities  of  the  feces. 

The  absence  of  a  nervous  etiologic  factor  only  rarely  helps  in  the 
differentiation,  because  almost  all  human  beings  have  been  subjected 
to  such  nervous  influences  as  may  cause  diabetes,  and  because 
nothing  is  more  common  than  an  hereditary  neurotic  predisposition. 
In  rare  cases  a  tumor  may  be  felt  in  the  pancreas  during  life. 
Icterus  also,  when  there  are  no  other  distinct  causes  for  it,  speaks 
for  disease  of  the  pancreas,  which  per  se  often  causes  icterus.  Then 
there  are  sometimes  colicky  pains  referable  to  the  pancreas  (not 
rarely  accompanied  by  vomiting  or  by  diarrhea)  (Fleiner,  Licht- 
heim,  Naunyn).  These  pains  may  increase  in  severity  for  hours, 
are  felt  in  the  epigastrium,  and  radiate  to  the  back.  Sometimes 
they  are  observed  in  cases  of  calculi  in  the  pancreatic  ducts,  and 
the  stones,  consisting  chiefly  of  phosphates  and  calcium  carbonate, 
may  be  passed  with  the  stools  (Minnich).  Often,  when  the  func- 
tions of  the  pancreas  are  impaired,  the  feces  contain  abnormal 
quantities  of  fat.  Such  stools,  conspicuous  by  their  light  color, 
strongly  suggest  a  pancreatic  origin.  Le  Nobel  also  considers  the 
absence  of  salts  of  the  fatty  acids  simultaneously  with  the  presence 
of  large  quantities  of  fat  as  characteristic  of  the  feces  in  cases  of 
pancreatic  diabetes.  As  the  pancreas  is  important  in  the  assimila- 
tion both  of  proteids  and  of  carbohydrates,  the  presence  in  the  feces 
of  abnormal  quantities  of  undigested  remains  of  both  of  these  kinds 
of  food  also  speaks  for  pancreatic  diabetes.  Finally,  Le  Nobel  lays 
stress  on  the  decrease  in  or  absence  from  the  feces  and  the  urine 
of  indol  and  skatol,  and  of  the  corresponding  series  of  products  of 
decomposition,  with  their  combined  sulphuric  acid,  in  pancreatic 
diabetes.  Naunyn,  in  his  recent  work,  also  mentions  the  late 
appearance  in  the   urine,    in   cases  of  pancreatic    diabetes,    of  the 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 35 

reaction  for  salicylic  acid  after  administration  of  salol,  which  sub- 
stance, under  the  influence  of  the  pancreatic  juice,  is  quickly  de- 
composed into  salicylic  acid  and  phenol.  Otherwise  the  urine 
affords  no  information  concerning  the  pancreas.  The  glycosuria, 
the  phosphaturia,  the  azoturia,  and  the  amounts  in  the  urine 
of  all  products  of  metabolism  are  exactly  the  same  in  pancreatic 
as  in  other  forms  of  diabetes.  Von  Ackeren's  and  Le  Nobel's 
maltosuria  seems  to  represent  a  mistake,  as  the  sugar  in  the  urine 
in  dogs  after  extirpation  of  the  pancreas  is  found  to  be  glucose 
(v.  Mering,  Minkowski),  and  as  many  other  pancreatic  cases 
afterward  observed  constantly  presented  glucose  in  the  urine.  The 
liver,  which  Lancereaux  first  described  as  unduly  large  in  neuro- 
genic, but  as  of  normal  size  in  pancreatic,  diabetes,  may,  as  he  now 
acknowledges,  be  equally  large  in  both  conditions.  It  must  further 
be  remembered  that  symptoms  referable  to  the  pancreas  need 
not  be  present  in  all  cases  of  pancreatic  diabetes.  Neither  need 
pancreatic  or  neurogenic  diabetes  always  be  the  severe  type  ;  it  has 
been  proved  that  severe  lesions  of  the  pancreas,  as  of  the  nervous 
system,  may  cause  mild  diabetes.  In  practice,  many  cases  are  en- 
countered in  which  it  is  quite  impossible  to  decide  between  pan- 
creatic and  neurogenic  diabetes. 

Fully  two  hundred  years  elapsed  between  Brunner's  original 
attempt  at  extirpation  of  the  pancreas  (1686)  and  Minkowski's  and 
v.  Mering's  discovery  of  the  glycosuria  resulting  from  that  opera- 
tion. Yet  Cowley,  in  1788,  noted  atrophy  of  the  pancreas  due  to 
concretions  in  a  case  of  diabetes,  and  Haller  observed  intense 
hunger  after  extirpation  of  the  pancreas.  Within  more  recent 
tirnes  Bouchard,  in  185 1,  expressed  his  opinion  of  a  causal  con- 
nection between  diseases  of  the  pancreas  and  diabetes,  and  Lance- 
reaux's  three  cases  (1877)  established  the  matter  in  the  mind  of  the 
profession.  Later,  N.  Senn  observed  several  symptoms  of  dia- 
betes in  dogs  after  extirpation  of  the  pancreas,  and  William  T. 
Bull,  after  such  an  operation  on  a  patient,  observed  diabetes.  Both 
of  these  distinguished  American  surgeons,  however,  were  con- 
cerned chiefly  with  the  surgical  features  of  their  work,  and  they  just 
missed  adding  a  great  discovery  in  experimental  pathology  to  their 
other  successes.  The  same  fate  befell  Finkler  and  Orth,  who  had 
undertaken  extirpation  of  the  pancreas  in  dogs  in  order  to  observe 


136  DIABETES    MELLITUS    AND    GLYCOSURIA. 

any  possible  diabetic  effect.  They  evidently  failed  in  their  purpose 
by  not  effecting  complete  extirpation.*  Finally,  v.  Mering  and 
Minkowski,  in  1889,  announced  their  great  discovery  at  Strasburg. 
If  we  have  been  rather  slow  in  acquiring  facts,  some  of  us,  how- 
ever, are  really  much  too  quick  in  drawing  conclusions,  and  there  are 
some,  especially  in  France,  who  consider  that  all  cases  of  diabetes  are 
of  pancreatic  origin,  and  who,  as  soon  as  glycosuria  is  mentioned,  at 
once  think  of  the  pancreas,  as  quickly  as  they  do  of  alcohol  when 
delirium  tremens  is  referred  to.  The  clinician,  however,  who  learns 
that  a  broker  was  attacked  by  diabetes  after  great  losses,  a  statesman 
after  a  political  failure,  a  woman  after  the  loss  of  her  husband,  and 
any  one  after  a  severe  blow  on  the  neck,  will  scarcely  believe  that  this 
effect  has  been  brought  about  by  the  pancreas ;  and  when  one  finds 
postmortem  that  the  pancreas,  in  fully  nine  out  of  ten  cases,  after 
diabetes  is  either  normal,  macroscopically  and  microscopically,  or 
presents  no  greater  change  than  a  slight  degree  of  atrophy,  such  as 
is  found  in  many  other  organs,  he  does  not  gain  the  impression  that 
the  cause  of  diabetes  is  constantly  to  be  found  in  the  pancreas. 
Whatever  information  the  future  may  bring,  it  is  to-day  absurd  to 
insist  upon  a  primary  pancreatic  cause  for  every  case  of  diabetes, 
and  facts  rather  point  to  the  conclusion  that  pancreatic  diabetes 
represents  only  a  small  minority  of  all  cases  of  diabetes. 

Then  there  is  the  "constitutional,"  "fat,"  "gouty,"  or  "her- 
petic "  diabetes,  which  often  seems  to  be  a  distinct  type.  These 
designations  are  used  to  indicate  the  mild  cases  with  a  course  cov- 
ering many  years,  which  develop  slowly  in  middle  age  or  in  senility, 
and  which  often  constitute  rather  a  weakness  than  a  disease.  This 
condition  is  found  almost  exclusively  among  the  upper  classes,  and 
usually  among  brain-workers.  A  diabetic  of  this  kind  generally 
has  some  hereditary  neurotic,  gouty,  or  adipose  predisposition, 
which  may  have  developed  in  several  directions.  He  has  usually 
been  "  nervous  "  throughout  his  whole  life,  and  he  has  often  suf- 
fered in  youth  from  cutaneous  eruptions  (eczema,  Hchen,  psoriasis). 
In  middle -age  he  becomes  sedentary,  delights  in  the  pleasures  of 
the  table  (which  often  have  to  make  up  for  a  somewhat  lowered 
virility),  suffers    from    neuralgic,   rheumatic,  and    gouty   troubles, 

*  Medical  Congress  at  Wiesbaden, »i 886. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 3/ 

and  begins  to  show  glycosuria,  which  may  amount  to  a  mild  dia- 
betes, with  slight  dystrophic  troubles,  cutaneous  eruptions,  fur- 
uncles, neuritis,  brittle  nails,  defective  teeth,  etc.  With  many  of 
these  patients,  especially  those  that  suffer  from  gout,  the  chances 
of  reaching  advanced  age  are  almost  as  good  as  with  the  average 
man,  and  their  diabetes  continues  to  be  slight.  An  affection  that 
begins  as  a  "constitutional"  diabetes  may,  however,  in  rare  cases, 
later  appear  as  a  neurogenic  one  ;  neither  is  it  perfectly  certain  that 
such  an  affection  does  not  depend  upon  changes  in  the  pancreas. 

It  is  impossible  at  present  to  decide  what  is  hepatogenic  diabetes  ; 
it  is  not  even  quite  certain  that  this  designation  may  not  be  applica- 
ble to  all  varieties  of  diabetes.  In  equal  degree  muscular  diabetes 
is  a  mystery.  Gastro-intestinal  diabetes — with  all  respect  to  the 
honored  name  that  first  advocated  this  designation — according  to 
all  evidence  does  not  exist  at  all.  Renal  diabetes  is  not  deserving 
of  the  name  diabetes,  and  has  been  mentioned  among  the  glyco- 
surias. 


Bronze-colored  Diabetes.* 

Since  1882,  when  a  treatise  by  Hanot  and  Chaufifard  appeared,t 
about  a  dozen  cases  of  a  most  peculiar  form  of  diabetes  have 
been  described,  almost  all  of  which  have  occurred  in  France. 
This  form  of  diabetes  offers,  cHnically,  a  good  deal  of  resem- 
blance to  pancreatic  diabetes,  but  it  is  apparently  a  disease  sui 
generis,  and  is  called  "  le  diabete  bronzee,"  from  the  color  of  the 
patient's  skin.  Bronze-colored  diabetes  generally  appears  in  men 
between  forty  and  sixty  years  old ;  in  most  cases  there  has 
been  a  previous  history  of  alcoholism  or  malaria.  It  presents  the 
clinical  picture  of  a  severe  diabetic  syndrome,  and  is  usually  com- 
plicated with  tuberculosis.  In  addition,  there  may  be  marked 
dyspeptic  symptoms,  considerable  swelling  of  the  abdomen,  with  a 
small  amount  of  ascites,  a  hypertrophic,  hard,  and  sensitive  liver, 
some  dilatation  of  the  abdominal  veins    (rarely  a  distinct    "  caput 


*"La  Cachexie  Bronzee  dans  le  Diabete,"  Gonsalez  Hernandez,  Th6se,  Mont- 
pellier,  1892.  Pierre-Marie,  "  Sem.  Med.,"  1895.  Brault  and  Gallard,  Letulle,  and 
others. 

t  "Revue  de  Med." 
10 


138  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Medusae "  around  the  umbilicus),  high-colored  urine,  and  pro- 
nounced cachexia.  The  most  conspicuous  symptom  of  all,  how- 
ever, is  a  dark  brownish-gray  color  of  the  whole  skin,  most  pro- 
nounced in  the  face,  on  the  extremities,  and  on  the  genitals. 

The  disease  invariably  leads  to  death — usually  in  marasmus  or 
coma — in  about  a  year's  time. 

Besides  the  usual  diabetic  changes,  almost  all  of  the  organs,  but 
chiefly  the  liver,  the  pancreas,  the  walls  of  the  alimentary  canal,  and 
the  mesenteric  glands,  are  found  the  seat  of  an  abundant  ocher- 
colored  deposit,  derived  from  the  hemoglobin  of  the  blood.  This 
substance  increases  up  to  several  thousand  per  cent,  the  amount  of 
iron  of  the  tissues  (Hanot,  Lapique,  Parmentier  and  Carrion). 
(The  same  pigment  is  present  in  the  malarial  cachexia,  in  hyper- 
trophic cirrhosis  of  the  liver,  and  in  Addison's  disease.)  The  liver 
is  found  in  a  state  of  diffuse  hypertrophic  cirrhosis  with  pigmented 
cells.  Its  arteries  are  almost  occluded  as  a  result  of  endarteritis 
(Triboulet),  and  the  portal  system  is  remarkably  dilated.  Other 
organs  also  are  often  more  or  less  cirrhotic.  The  red  blood- 
corpuscles  are  diminished  in  number ;  Parmentier  and  Carrion 
found  about  3,500,000  to  the  cubic  millimeter.  Several  observers — 
e.  g.,  Anselme — consider  the  disintegration  of  the  red  blood- 
corpuscles  from  some  unknown  cause  responsible  for  the  diabetes 
by  invading  the  pancreas  and  inducing  cirrhosis. 

I  have  already  mentioned  that  habitual  excretion  of  glucose, 
however  inconsiderable,  generally  becomes  permanent,  in  so  far  that 
it  occurs  daily  for  some  time  after  meals  ;  and  that  simple  glyco- 
suria usually  remains  unchanged,  though  there  are  exceptions  to  this 
rule. 

In  cases  of  true  diabetes  definitive  cessation  of  glycosuria  with  a 
free  diet  is  still  rarer,  and  such  complete  and  permanent  restoration 
to  health  certainly  does  not  occur  in  more  than  about  one  per  cent, 
of  all  cases.  I  think  it  likely  that  this  occurs  chiefly  in  cases  in 
which  the  diabetes  has  been  caused  by  trauma  or  by  infection,  and 
that,  when  it  takes  place,  the  restoration  is  effected  within  a  com- 
paratively short  time. 

One  often  hears  patients,  and  sometimes  physicians,  speak  of 
recovery  from  diabetes  and  restoration  to  complete  health.   Almost 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 39 

all  such  reports  will  be  found  incorrect  on  careful  investigation. 
Sometimes  the  glucose  has  disappeared  with  a  restriction  of  carbo- 
hydrates and  reappears  with  a  free  ordinary  diet.  In  other  cases 
transitory  or  periodic  increase  in  the  power  of  assimilation  is  re- 
sponsible for  the  mistake  (see  Periodic  Diabetes).  Other  reports  of 
like  character  refer  to  simple  transitory  glycosuria  from  some  acci- 
dental cause,  or  even  to  the  casual  occurrence  in  the  urine  of 
reducing-substances  other  than  glucose. 

I  have,  in  practice,  seen  disappearance  of  glucose  from  the  urine 
with  a  free  diet  only  in  three  cases  in  which  sugar  had  appeared  * 
in  diabetic  quantities.  In  one  of  these  cases  there  remained  a  dis- 
tinct polyuria, — i.  e.,  diabetes  insipidus, — as  has  happened  in  several 
reported  cases. 

My  first  case  of  recovery  from  diabetes  was  the  one  following 
influenza  mentioned  under  glycosuria  due  to  infection.  Both  the 
fully  developed  diabetes  and  the  restoration  of  normal  conditions 
for  at  least  several  months  appear  to  me  to  be  certain. 

The  second  case  was  that  of  a  Scandinavian  lady,  fifty-one  years 
old,  who,  after  a  violent  blow  on  the  forehead,  felt  exceedingly 
weak,  and  lost  in  weight  for  a  considerable  time.  She  did  not 
remember  any  symptoms  of  diabetes  other  than  pruritus  vulvae. 
After  a  year  and  a  half  she  at  last  consulted  a  physician,  who  found 
the  urine  to  have  a  specific  gravity  of  1.037,  and  to  contain  a  large 
amount  of  glucose  ;  the  presence  of  the  latter  was  ascertained  by  a 
fully  reliable  investigation.  When  I  saw  the  patient,  half  a  year 
later,  there  was  nothing  noteworthy  beyond  some  neurasthenic 
symptoms  and  a  cataract  in  drop-form,  which  probably  had  nothing 
to  do  with  diabetes.  After  five  days  of  free  diet  with  a  consider- 
able amount  of  carbohydrate  the  urine  did  not  contain  glucose ; 
nor  was  there  any  pathologic  trace  of  it  in  the  urine  collected  for 
six  hours  after  ingestion  of  120  grams  of  glucose.  Some  time 
before  this  was  written,  three  and  a  half  years  after  her  accident, 
the  patient  appeared  to  tell  me  of  her  complete  recovery.  She  has 
observed  no  dietetic  rules,  but  the  urine  has  always  been  found  free 
from  sugar,  and  is  so  at  present. 

*  I  have  seen  rather  large  quantities  of  glucose  (for  simple  glycosuria)  in  typhoid 
fever  disappear  after  the  end  of  the  fever,  and  I  have  seen  diabetic  quantities  of  glucose 
after  influenza  dwindle  to  simple  glycosuria. 


140  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  third  case  was  Mr.  F.  D.,  a  teacher  from  Boston,  forty-five 
years  old,  who  had,  five  months  previously,  without  manifest  cause, 
been  seized  with  symptoms  of  diabetes  ;  a  chemist  of  Harvard  Uni- 
versity had  found  7.5  per  cent,  of  glucose  in  a  specimen  of  his 
urine.  The  patient  had  for  three  months  before  arriving  at  Carls- 
bad observed  a  most  rigorous  diet.  Under  my  care  he  gradually 
received  an  increased  supply  of  carbohydrates,  until  more  than  two 
hundred  grams  a  day  were  given.  The  urine,  which  contained  no 
albumin,  remained  free  from  glucose  during  his  four  weeks'  stay  in 
Carlsbad ;  but  the  quantity  reached  three  liters  a  day,  and  the 
specific  gravity  was  about  1.012. 

Thus,  it  sometimes,  though  rarely,  happens  that  a  true  diabetic 
may  be  restored  to  health.  Whether  this  ever  happened  in  a  case 
of  severe  diabetes  is  another  matter  ;  so  far  as  I  know,  not  one  cer- 
tain instance  of  this  kind  has  been  recorded.  In  my  own  experi- 
ence, I  have  never  seen  any  case  with  diacetic  acid  (apart  from 
inanition  and  in  association  with  a  full  supply  of  food)  in  which  this 
acid  has  disappeared.* 

Mild  diabetes  is  compatible  with  long  life,  and  I  know  of  cases 
that  in  all  probability  have  lasted  forty  years,  and  with  certainty 
more  than  thirty  years.  A  duration  of  twenty  years  is  by  no  means 
rare.  The  outlook  is  the  better,  the  later  in  Hfe  the  disease  sets  in, 
the  greater  the  power  of  assimilating  carbohydrates,  and  the  better 
the  general  somatic  and  mental  state.  A  strong  digestion  is  of  very 
favorable  moment.  Trauma  and  infection  as  causes  afford  a  better 
prognosis  with  regard  to  both  complete  recovery  and  a  mild  course. 
Gout  and  adiposity  as  complications  are  favorable  signs,  especially 
gout.  Heredity  does  not  seem  to  me  so  pernicious  an  influence  as 
some  authorities  would  make  it.  I  have  at  least  several  times  seen 
sons  of  diabetic  fathers  or  mothers  present  through  many  years 
mild  diabetes  or  simple  glycosuria.  Independent  pecuniary  re- 
sources and  the  ability  to  live  without  care  in  a  suitable  climate, 
and  to  afford  a  generous  diet,  are  highly  advantageous  to  the  dia- 
betic patient. 

*Dr.  Toepfer,  of  Carlsbad,  has  told  me  of  such  a  case  in  a  young  diabetic  girl,  who 
one  summer  presented  a  distinct  Gerhardt's  reaction,  even  while  increasing  in  weight, 
and  who  the  following  summer  exhibited  no  diaceturia.  Such  an  occurrence  is  certainly 
exceedingly  rare. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  I4I 

Mild  diabetes  more  commonly  remains  mild  diabetes  than  it 
develops  into  severe  diabetes.  On  the  other  hand,  a  transition 
from  the  mild  into  the  severe  stage  is  no  very  rare  occurrence,  and 
it  is  difficult  to  understand  how  even  specialists  of  wide  experience 
can  have  failed  to  observe  it. 

Severe  diabetes  rarely  lasts  more  than  four  or  five  years  ;  the 
average  duration  can  not  be  much  above  three  years.  In  very 
severe  cases,  and  especially  in  young  persons  (see  below),  the 
dystrophy  may  lead  to  death  in  a  few  weeks. 

I  make  the  following  twenty-four  extracts  from  my  records  of  diabetic 
patients.  The  cases  are  related  as  briefly  as  possible,  and  they  are  intended 
only  to  convey  an  impression  of  the  general  clinical  picture  of  the  diabetic 
syndrome  and  its  common  complications.  The  cases  are  arranged  so  as  to 
represent  different  stages  and  to  illustrate  the  gradual  failure  of  the  power  of 
assimilation  and  the  development  of  the  glycosuric  dystrophy.  If  one  is 
anxious  for  appellations,  he  may  call  the  first  8  cases  simple  glycosuria,  the  next 
8  cases  mild  diabetes,  and  the  last  8  severe^diabetes,  at  the  time  when  last  in- 
vestigated. Matters  of  local  significance,  of  nationality,  of  treatment,  etc.,  are 
here  omitted.  The  patients  include  Scandinavians,  Americans,  Germans,  and 
Englishmen  ;  the  first  alone  belonged  to  the  Semitic  race. 

1.  Mr. ,  thirty -two  years  old,  came  to  Carlsbad  with  dyspeptic  troubles, 

which  showed  themselves,  however,  to  be  only  the  gastric  manifestations 
of  a  pronounced  neurasthenia,  partly  inherited  and  partly  acquired,  chiefly 
through  sexual  excesses.  The  patient  had  of  late  years  grown  exceedingly 
"  nervous."  His  restless  sleep  was  of  the  usual  neurasthenic  type,  with  an  in- 
terruption of  complete  wakefulness  from  i  to  4  or  5  A.  m.  The  man  was 
irritable,  often  giddy,  had  a  "  casque  neurasthenique,"  a  beautifully  pro- 
nounced "plaque  sacree  "  and  other  rhachialgic  manifestations,  shooting-pains 
in  the  legs  after  standing  for  some  minutes,  etc.  The  usual  fear  of  suspected 
tabes  was  (as  always)  entirely  unfounded  ;  thorough  investigation  demon- 
strated, even  to  the  patient's  satisfaction,  the  absence  of  all  symptoms  of  that 
disease,  and,  rather  strangely,  he  had  escaped  syphilis.  The  man  declared 
somewhat  mournfully  that  coitus  was  no  longer  "  what  it  had  been,  what  it 
could  be,  and  what  it  ought  to  be";  besides,  the  act  had  been  of  late  suc- 
ceeded by  a  feeling  of  extreme  weakness. 

The  urine  obtained  one  hour  after  the  end  of  dinner  constantly  underwent 
reduction,  which  disappeared  after  fermentation.  When  reduction  was  most 
marked,  the  urine  caused  a  slight  deflection  of  the  ray  of  polarized  light  to  the 
right  instead  of  the  customary  deflection  to  the  left  (from  combined  glycuronic 
acid). 

2.  Miss ,  twenty  years  old,  had  been  informed  by  her  physician,  eight 

years  previously,  that  her  urine  contained  sugar.  There  was  no  direct  hereditary 


142  DIABETES    MELLITUS    AND   GLYCOSURIA. 

cause  and  no  etiologic  point  other  than  some  intellectual  overwork  and  a  dis- 
appointment in  love  just  before  the  discovery  of  the  glycosuria. 

At  sixteen  the  patient  had  hysteric  attacks  and  several  stigmata.  She  was 
of  a  marked  nervous  temperament,  and  suffered  still  from  periods  of  sleepless- 
ness, "terreur  nocturne,"  and  other  manifestations  of  similar  character. 
Sometimes  during  nervous  exacerbations  the  patient  herself  was  cognizant  of 
polyuria  and  pollakiuria,  with  the  almost  colorless  ("  spastic  ")  urine  secreted 
periodically  by  "  nervous  "  persons. 

When  the  young  woman  consulted  me  she  was  at  her  best,  and  made  the 
impression  of  a  lively,  fairly  healthy  individual,  with  no  distinct  hysteric* 
and  only  moderate  neurasthenic  symptoms,  and  presenting  nothing  remarka- 
ble apart  from  the  urine,  which  repeatedly,  in  samples  obtained  an  hour  after 
meals,  contained  from  0.05  to  0.2  per  cent,  of  glucose.  On  a  perfectly  free 
mixed  diet  the  tall  young  woman  passed  1850  cu.  cm.  of  urine,  with  a  specific 
gravity  of  1.021  and  a  faint  trace  of  glucose.  Eight  years  after  the  discovery 
of  the  glycosuria  I  learn  that  the  state  has  not  changed,  and  that  the  general 
health  is  fairly  good. 

3.  Mr.  J.,  fifty-nine  years  old,  had  a  diabetic  father,  had  himself  worked 
hard  intellectually  for  a  large  part  of  his  life,  felt  a  strong  attraction  to  the  fair 
sex,  and  thought  American  whisky  a  most  delightful  and  wholesome  bev- 
erage. He  had  been  a  hard  smoker.  The  still  deeply  affected  father  was 
scarcely  able  to  mention  the  terrible  loss  of  a  daughter  two  and  a  half  years 
before. 

The  patient  came  to  Carlsbad  for  adiposity  and  gout  (in  the  big  toe  !).  Sleep 
was  fairly  good ;  sexual  power,  considering  age,  likewise ;  and  the  knee-jerk 
present.  The  heart  was  somewhat  weak,  with  distant  sounds  ;  the  organ  was 
somewhat  enlarged,  the  pulse  small  and  weak,  but  fairly  regular.  The  func- 
tions in  general  were  tolerably  well  performed,  and  after  a  mild  dietetic  course 
and  systematic  exercises  the  patient  took  quite  long  walks  in  the  hills  around 
Carlsbad.     The  teeth  were  partly  absent  and  partly  affected  with  caries. 

On  the  back  a  gouty  eczema  existed. 

The  ophthalmoscope  disclosed  a  distinct  picture  of  optic  neuritis,  chiefly 
marked  on  the  right  side  (from  tobacco  and  whisky). 

The  patient  assured  me  that  his  urine,  recently  analyzed,  was  normal. 
Finding  him  a  sensible  and  not  at  all  a  hypochondriac  person,  I  told  him  that, 
from  his  "tout  ensemble,"  I  was  quite  certain  that  during  some  parts  of  the 
day  it  would  contain  small,  clinically  insignificant,  but  abnormal  quantities 
of  glucose — and  a  specimen  obtained  after  dinner  contained  about  0.25  per 
cent. 

4.  Dr.  X,  a  physician,  was  descended  from  families  both  of  which  were  free 
from  developed  psychoses,  but  which,  together  with  some  instances  of  great  in- 
tellectual capacity,  included  others  of  "  eccentricity  "  and  extremely  choleric 
temperament. 

*  The  field  of  vision  was  not  examined. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 43 

The  patient  himself  was  strong,  but  sensitive  and  lively  as  a  child.  He  had 
suffered  now  and  then  from  eczema,  and  had  worked  hard  and  participated  a 
good  deal  in  the  customary  dissipations  at  the  university.  At  the  age  of  twenty- 
three  he  was  subjected  to  a  powerful  depressing  emotion,  and  some  weeks 
afterward  a  series  of  furuncles  appeared.  The  patient  at  this  time  worked 
hard  for  academic  honors,  and  a  year  later  began  to  suffer  from  sleeplessness ; 
diminution  in  sexual  desire  and  other  neurasthenic  symptoms  developed.  At 
twenty-five  the  patient  for  the  first  time  accidentally  found  a  distinct  trace  of 
sugar  in  his  urine  ;  this  again  happened  when  he  had  reached  his  thirty-second 
year.  He  then  alsb  found  distinct  oxaluria.  Shortly  afterward  the  patient,  at 
a  postmortem  examination,  contracted  a  severe  pyemia,  which  wrecked  him 
somatically  and  depressed  him  mentally  for  some  time.  At  the  age  of  thirty- 
eight  the  patient  again  accidentally  found  sugar  in  his  urine,  and  in  view  of 
the  two  previous  observations  of  the  same  kind,  subjected  himself  to  a  thorough 
investigation.  It  was  then  found  that  a  liberal  supply  of  carbohydrates  (sev- 
eral hundred  grams)  did  not  cause  sufficient  glycosuria  to  permit  a  distinct 
reaction  with  Nylander's  solution  of  the  urine  for  the  twenty-four  hours,  which 
amounted  to  between  1500  and  1800  cu.  cm. ;  that  the  first  specimen  obtained 
an  hour  after  dinner  usually  contained  between  o.i  and  0.2  per  cent,  of  glu- 
cose ;  that  the  patient  generally  could  take  a  large  amount  of  rice  or  300  grams 
of  cane-sugar  without  the  development  of  glycosuria  ;  and  that  the  slight  amount 
of  glucose  that  appeared  in  the  urine  after  mixed  meals  with  some  wine  could 
temporarily  be  increased  quite  considerably  under  the  influence  of  emotional 
disturbances.  On  one  occasion  the  patient,  immediately  after  a  rather  sump- 
tuous dinner,  was  seized  with  an  intense  fit  of  anger ;  a  specimen  of  urine 
passed  shortly  afterward  contained  1.4  percent,  of  glucose,  the  largest  quantity 
observed  among  more  than  100  analyses,  of  which  only  one  other  had  yielded 
so  much  as  0.4  per  cent.  The  patient  now  for  three  days  lived  chiefly  on  carbo- 
hydrates ;  then  collected  the  urine  for  twenty-four  hours,  and  to  his  delight  saw 
the  phosphates  form  a  beautifully  white  precipitate  on  boiling  with  Nylander's 
solution.  But  few  analyses  have  since  been  made,  and  these  showed  speci- 
mens of  the  urine  collected  for  twenty-four  hours  to  be  practically  free  from 
glucose.  The  patient  has  presented  gouty  symptoms  from  his  thirty-third  year. 
The  joints  of  the  fingers  from  time  to  time  suddenly  swell  and  become  tender. 
The  great  toe  of  the  right  foot  also  has  been  involved.  Dr.  X  is  now  (1899) 
in  his  fifty-second  year,  and  is  rather  healthier  than  twenty  years  ago.  He  is 
unwilling  to  permit  further  analysis,  which  formerly  kept  him  in  a  hypochon- 
driac state.  His  weight  keeps  at  the  level  of  95  kilograms.  The  patient  was 
married  eighteen  years  ago,  and  has  six  mostly  strong  and  healthy  children. 
One  otherwise  healthy  child  suffered  for  a  long  time  from  nocturnal  enuresis 
and  from  psoriasis. 

Another  physician,  an  apparently  healthy,  hard-working  man,  on  hearing 
of  Dr.  X's  glycosuria,  mentioned  the  fact  that  he  had  himself  accidentally 
found  sugar  in  his  own  urine  sixteen  years  ago.  An  hour  had  just  passed  since 
his  frugal  dinner  when  this  was  mentioned.  I  expressed  my  opinion  that  the 
urine  probably  still  contained  glucose,  and  we  found  fully  0.2  per  cent,  of  it  in 
the  specimen. 


144  DIABETES    MELLITUS   AND    GLYCOSURIA. 

5.  An  apothecary,  forty-eight  years  old,  whose  father  had  suffered  for 
many  years  in  old  age  from  diabetes,  was  terrified  by  finding  sugar  in  his  own 
urine. 

The  patient  presented  the  outward  appearance  of  an  unusually  healthy, 
powerful  man.  During  the  preceding  ten  years  his  weight  has  kept  at  about 
107  kilograms,  and  his  height  was  about  six  feet.  Investigation  failed  to  dis- 
close anything  abnormal.  Even  most  of  the  usual  neurasthenic  symptoms 
were  absent,  except  a  fear  of  approaching  great  depths  and  slight  weakening  of 
sexual  power. 

The  urine  was  collected  several  times  for  twenty-four  hours,  with  an  allow- 
ance of  120  grams  of  white  bread  and  some  green  vegetables  in  the  diet.  The 
secretion  varied  from  870  to  1200  cu.  cm.  in  amount,  and  from  1.033  ^o  '^•023 
in  specific  gravity.  A  specimen  of  the  twenty-four  hours'  urine  contained 
scarcely  so  much  as  0.05  per  cent,  of  glucose. 

The  patient  took  300  grams  of  cane-sugar  in  one  liter  of  Giesshiibler  water, 
and  after  four  and  a  half  hours  the  urine  was  found  free  from  glucose.  The 
amount  collected  equaled  500  cu.  cm.,  with  a  specific  gravity  of  1.016,  and  it 
contained  about  0.05  per  cent,  of  glucose.  After  being  boiled  with  sulphuric 
acid  the  urine  reduced  as  a  solution  of  0.24  per  cent,  of  glucose. 

6.  Mr.  G.  W.,  a  bank  clerk,  fifty-six  years  old,  was  free  from  known 
hereditary  predisposition  or  other  etiologic  influence  worthy  of  mention  other 
than  a  severe  malaria  thirty  years  before.  He  came  to  Carlsbad  on  account 
of  constipation,  which,  together  with  flatulence,  constitutes  his  chief  complaint. 
He  was  a  fat,  exceedingly  "nervous"  man,  with  a  melancholy,  "fussy"  tem- 
per ;  had  a  pronounced  "  casque  neurasthenique  "  ;  slept  badly  ;  did  not  like 
to  go  out  on  a  balcony  ;  had  weak  sexual  power ;  and  was  easily  made  tired  by 
physical  or  intellectual  exertions. 

I  found  glucose  in  the  urine,  which  contained,  besides,  many  crystals  of 
calcium  oxalate.  The  patient  ate  nearly  300  grams  of  bread  a  day,  and  what- 
ever he  liked  besides.  A  specimen  of  urine  an  hour  after  dinner  contained 
I.I  per  cent,  of  glucose  ;  but  the  mixed  total  quantity  for  twenty-four  hours, — 
1500  cu.  cm.,  with  a  specific  gravity  of  1.024, — not  quite  o.i  per  cent. 

The  patient  told  me  five  years  afterward  (in  Stockholm)  that  he  went  to 
Lindewiese,  in  Silesia,  and  lived  exclusively  on  white  bread,  and  that  the 
sugar  then  disappeared  from  his  urine.  Investigation,  however,  proved  the 
state  to  be  exactly  what  it  had  been  in  Carlsbad. 

7.  Mr. ,  forty-six  years  old,  a  noted  barrister,  came  to  Carlsbad  on  ac- 
count of  dyspeptic  troubles  and  not  excessive  adiposity — he  weighed  94  kilo- 
grams. The  condition  was  much  like  that  described  in  case  3.  The  patient 
had  hereditary  adipose  and  gouty  tendencies  ;  had  worked  hard  and  smoked 
hard;  had  led  a  sedentary  life  and  greatly  enjoyed  a  good  table.  He  was 
quite  irritable,  slept  badly,  and  had  incipient  symptoms  of  smoker's  heart. 
I  found  0.4  per  cent,  of  glucose  in  a  specimen  of  urine  after  dinner.  Free 
diet  is  attended  with  the  elimination  of  a  normal  quantity  of  a  somewhat 
"  lithemic  "  urine,  containing  a  distinct  trace  of  sugar. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 45 

Seven  years  afterward  I  saw  the  patient  in  his  home.  He  was  very  active  in 
his  profession,  had  made  a  large  fortune  by  speculation,  and  did  not  know 
anything  about  his  glycosuria,  suffering  only  from  slight  neurasthenic  symp- 
toms. 

Nine  years  after  our  first  acquaintance  I  again  saw  the  patient.  He  had 
worked  and  speculated  a  great  deal,  had  twice  made  and  lost  a  large  fortune, 
and  had,  still  more  than  before,  led  a  life  of  constant  emotional  activity.  The 
former  simple  glycosuria  now  sometimes  reached  diabetic  figures  (two  per 
cent.)  in  large  specimens,  and  occasionally  slight  symptoms  of  diabetes  mani- 
fested themselves. 

8.  Professor ,  fifty-eight  years  old,  a  distinguished  surgeon,  had  had  a 

rheumatic  and  gouty  father,  and  had  himself,  eleven  years  before,  discovered 
two  per  cent,  of  glucose  in  a  specimen  of  his  urine,  having  for  some  time  pre- 
viously felt  tired  and  worn  out. 

A  specimen  of  urine  after  a  dinner  with  a  moderate  supply  of  carbohydrates 
had  a  specific  gravity  of  1.037,  but  was  found  (by  titration  and  polarization)  to 
contain  only  0.25  per  cent,  of  glucose.  With  a  customary  diet  and  some  re- 
striction of  carbohydrates  the  urine  amounted  only  to  somewhat  more  than  a 
liter,  with  a  specific  gravity  of  1.024  and  somewhat  more  than  o.i  per  cent,  of 
glucose. 

The  patient  was  slightly  neurasthenic  and  distinctly  "lithemic."  Some 
trouble  with  the  toes,  especially  the  great  toes,  probably  was  of  a  gouty 
nature. 

9.  Mr.  E.,  judge,  forty-seven  years  old,  belonged  to  a  family  with  strong 
neurotic  tendencies,  including  several  instances  of  diabetes.  The  patient  had 
in  his  youth  been  addicted  to  masturbation,  and  several  years  afterward  suf- 
fered from  neurasthenia.  Six  years  before  coming  under  observation  he  had 
applied  for  life-insurance,  but  was  refused  on  account  of  the  presence  of 
glucose  in  the  urine.  Shortly  afterward  he  was  seized  with  a  violent  attack  of 
influenza,  and  during  convalescence  a  specimen  of  urine  obtained  after  dinner 
contained  3.2  per  cent,  of  glucose. 

The  patient  was  a  heavily  built  man,  who  had  recently,  with  rigorous  dietetic 
restrictions,  lost  in  weight.  Finding  that  this  regime  affected  his  general 
health  badly,  he  returned  to  a  somewhat  more  liberal  diet,  with  a  moderate 
allowance  of  carbohydrates,  felt  considerably  better,  and  regained  his  previous 
weight.  There  were  no  distinct  diabetic  symptoms  except  the  glycosuria.  Even 
the  teeth  were  normal.  There  was  a  moderate  degree  of  neurasthenia,  with 
some  disturbance  of  sleep,  and  other  cerebrasthenic  symptoms.  The  sexual 
power  was  somewhat  impaired.  There  were  five  healthy  children  in  the 
family. 

A  perfectly  free  diet  without  any  restriction  whatever,  and  with  quite  a  large 
quantity  of  carbohydrates,  was  attended  with  the  secretion  of  1300  cu.  cm., 
with  a  specific  gravity  of  1.025  ^^d  0.28  per  cent,  of  glucose.  A  specimen 
obtained  after  dinner  contained  1.34  per  cent,  of  glucose.  The  patient  was 
again  put  on  a  systematically  but  moderately  restricted  diet,  and  the  urine  con- 


146  DIABETES    MELLITUS    AND    GLYCOSURIA. 

tained  only  traces  of  glucose.     Ten  years  after  the  discovery  of  the  mild  dia- 
betes I  again  met  the  patient  and  found  the  general  state  unchanged. 

10.  Dr.  H.,  a  widely  known  physician,  at  the  age  of  twenty-seven  years  acci- 
dentally discovered  over  two  per  cent,  of  glucose  in  a  specimen  of  his  urine. 
There  was  no  hereditary  influence,  but  a  history  of  much  intellectual  effort.  Nor 
were  there  other  symptoms  of  diabetes.  The  quantity  of  urine  had  always 
been  rather  large,  though  it  had  never  amounted  to  distinct  polyuria.  The 
patient  kept  himself  under  some  dietetic  restriction,  and  the  glycosuria  disap- 
peared for  several  years  and  did  not  reappear  even  upon  a  free  diet.  Six  years 
after  its  first  discovery  the  glycosuria  again  appeared,  following  an  attack  of 
typhoid  fever,  and  sometimes  reaching  considerable  proportions. 

Fourteen  years  have  now  elapsed  since  the  sugar  first  appeared  in  the  urine. 
The  patient,  a  man  of  iron  will,  adheres  constantly  to  a  diet  with  an  allow- 
ance of  about  seventy  grams  of  carbohydrate  a  day,  and  is  free  from  deter- 
minable glycosuria.  When  for  experimental  purposes  a  greater  allowance  is 
made,  the  sugar  again  appears  in  moderate  but  quite  determinable  quantities. 
This  most  valued  friend  of  mine,  who  is  a  hard  worker,  suffers  from  no  other 
symptom  than  periodic  insomnia. 

11.  Lieutenant-Colonel  R.,  a  retired  officer,  eighty-one  years  old,  has  no 
knowledge  of  hereditary  or  other  morbid  predisposition.  Thirty-nine  years 
before  coming  under  observation  the  man  suddenly  had  a  succession  of  fur- 
uncles, and  he  dates  his  diabetes  from  this  time  ;  the  glycosuria,  however,  was 
not  discovered  until  sixteen  years  later. 

The  patient,  who  has  been  under  my  care  for  many  years,  is  at  the  present 
time  (1899)  a  lively  old  gentleman,  with  a  healthy  appearance.  Only  during 
the  last  two  years  has  he  observed  any  failure  of  memory  ;  he  has  also  pru- 
dently left  off  playing  whist,  in  which  pastime  he  was,  up  to  his  eightieth  year, 
considered  to  have  few  equals.  The  patient  suffers  from  insomnia.  Some- 
times there  is  giddiness.  The  reflexes,  especially  the  knee-jerks,  are  weakened. 
Most  of  the  teeth  are  absent,  but  the  cavity  of  the  mouth  is  otherwise  normal. 
There  is  no  odor  of  acetone  from  the  breath.  The  patient  is  presbyopic,  but 
the  visual  acuity  is  fairly  good.  Gerontoxon  is  not  very  strongly  developed. 
There  is  some  slight  rigidity  of  the  radial  and  temporal  arteries. 

When  the  patient  partakes  of  a  moderate  but  undetermined  quantity  of 
bread  and  green  vegetables,  he  passes  about  two  liters  of  urine  containing 
about  two  per  cent,  of  glucose  or  a  little  more.  There  is  no  albuminuria. 
One  hundred  grams  of  Graham  bread  (about  forty  grams  of  carbohydrate)  and 
some  green  vegetables  yield  1750  cu.  cm.  of  urine,  with  a  specific  gravity  of 
1.025  and  containing  0.8  per  cent,  of  glucose. 

The  patient's  wife  also  suffers  from  mild  diabetes. 

12.  Baron  X,  fifty-eight  years  old,  a  statesman,  had  a  gouty  inheritance; 
his  mother  also  probably  suffered  for  many  years  from  diabetes.  The  patient 
has  for  forty  years  been  a  heavy  smoker,  and  had  been  much  interested  in  his 
good  table.     His  restless  spirit,  quarrelsome  temper,  and  heavy  responsibilities 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  14/ 

had  caused  him  a  life  full  of  emotions.  In  early  manhood  he  suddenly  in- 
creased considerably  in  weight.  Twenty-six  years  before  coming  under  obser- 
vation he  had  several  furuncles.  Already  at  this  period  his  teeth  began  to  show 
caries,  and  they  successively  fell  out ;  the  patient  had  often  suffered  from  gin- 
givitis. The  last  molar  tooth  was  sneezed  out  two  years  before  my  first  inves- 
tigation. The  glycosuria,  which  in  small  specimens  of  urine  has  reached  over 
six  per  cent,,  was  discovered  only  a  year  before  the  patient  came  to  me.  There 
was  no  albuminuria  and  no  diaceturia. 

The  patient  had  a  weak  nervous  system,  and  periodically  suffered  from  vio- 
lent supraorbital  neuralgia.  Some  years  previously  he  was  troubled  with 
agoraphobia  ;  he  always  carefully  shunned  steep  declivities.  Creeping  sensa- 
tions in  the  legs  and  nocturnal  cramps  in  the  calves  caused  annoyance. 
There  was  no  distinct  neuritis.     The  left  knee-jerk  was  weakened. 

The  spleen  was  somewhat  enlarged  (the  patient  had  had  malaria  eleven 
years  before).  The  liver  appeared  of  normal  size  on  percussion  and  palpation. 
The  heart  was  somewhat  large  and  not  powerful. 

During  two  seasons  in  Carlsbad  I  found  that  the  patient,  who  was  a  little 
less  unreliable  during  his  "cure"  than  at  home,  when  taking  120  grams  of 
white  bread  and  some  green  vegetables  with  his  food,  presented  a  gradual 
diminution  in  his  glycosuria,  until  in  the  third  week  he  was  passing  about  1800 
cu.  cm.  of  urine  containing  only  a  trace  of  sugar. 

13.  Herr  S,,  forty  years  old,  an  engineer,  had  some  months  previously 
suffered  from  a  remarkably  obstinate  ulcer  on  his  leg,  and  his  physician  found 
six  per  cent,  of  glucose  in  the  urine. 

The  patient  was  free  from  neurotic  or  diabetic  inheritance.  He  had  rarely 
neglected  free  libations  of  strong  grog  in  the  evening  and  had  smoked  im- 
moderately. During  the  preceding  few  years  he  had  suffered  from  gouty 
troubles.  Four  years  before  he  had  passed  through  a  violent  attack  of  influ- 
enza. The  patient  denied  syphilis,  but  his  wife  had  twice  miscarried  in  the 
sixth  month. 

The  patient  is  a  robust  man,  without  obvious  manifestations  of  theglycosuric 
dystrophy.  Even  the  cavity  of  the  mouth  exhibited  nothing  abnormal  beyond 
caries  of  two  teeth.  Sexual  power  was  rather  weak.  The  knee-jerks  were 
just  perceptible.     The  patient  now  and  then  felt  pain  "  deep  in  the  head." 

His  heart  was  somewhat  enlarged,  the  sounds  weak  and  distant,  the  impulse 
not  perceptible;  the  pulse  76,  not  quite  regular,  and  weak.  The  temporal 
arteries  were  unduly  distinct  on  palpation. 

One  hundred  grams  of  white  bread  and  some  green  vegetables  with  the 
food  yielded  regularly  about  2100  cu.  cm.  of  urine,  with  a  specific  gravity  of 
1.027  3.nd  containing  0.9  per  cent,  of  glucose,  a  trace  of  albumin,  and  some 
granulated  tube-casts.  After  two  days  of  abstinence  from  carbohydrates  the 
patient  was  able  to  take  regularly  sixty  grams  of  white  bread  a  day  with  green 
vegetables,  without  any  determinable  glycosuria. 

Nearly  three  years  after  this  the  patient  again  consulted  me.  He  had,  two 
weeks  before,  while  driving  about  in  a  cab,  suddenly  lost  first  his  sight  and 
shortly  afterward  consciousness,  having  previously  suffered  from  acute,  deep- 


148  DIABETES    MELLITUS    AND    GLYCOSURIA. 

seated  pains  in  his  head.  Consciousness  returned  after  some  hours.  There 
were  no  distinct  paretic  symptoms,  but  amblyopia  persisted  for  several  weeks. 
The  patient  could  at  first  only  count  fingers,  but  not  read.  Vision  gradually 
returned  to  the  previous  state.  The  patient's  physician  believes  the  symptoms 
to  have  been  due  to  uremia,  while  I  attribute  them  to  cerebral  hemorrhage. 
The  ophthalmoscope  disclosed  a  hemorrhagic  retinitis,  with  ecchymoses  in  dif- 
ferent stages.  The  glycosuria  was  now,  probably  in  consequence  of  the  cirrho- 
sis of  the  kidneys,  slighter  than  it  had  been  three  years  before  ;  120  grams  of 
white  bread  and  some  green  vegetables  causing  only  faint  traces  of  glucose  to 
appear  in  the  urine,  of  which  abouftwo  liters  were  excreted  in  the  twenty-four 
hours,  and  which  had  a  specific  gravity  of  1.021  and  contained  a  trace  of 
albumin. 

14.  A.,  a  restaurateur,  forty-seven  years  old,  developed  three  "  maux  per- 
forants  "  on  the  right  foot,  and  consulted  Dr.  H.  Toll,  who  found  a  large 
quantity  of  glucose  in  the  urine  and  called  me  in  consultation.  The  patient 
admitted  having  "wet  his  tongue  now  and  then,"  which  means  in  Sweden 
that  he  has  drunk  enormously. 

The  man  was  somewhat  maudlin,  slept  badly,  presented  no  knee-jerks, 
had  weakened  sexual  power,  and  complained  of  right  genitocrural  neuralgia. 
The  pupils  differed  distinctly  in  size.  The  patient  denied  all  history  of  syphilis. 
His  heart  was  somewhat  large,  his  pulse  small  and  weak,  but  regular.  Pro- 
nounced arteriosclerosis  was  obvious  in  the  radial,  temporal,  and  femoral 
arteries.     There  were  no  appreciable  signs  of  cirrhosis  of  the  liver. 

Restriction  of  the  diet  caused  disappearance  of  the  glycosuria  and  of  the 
distinct  polyuria,  and  the  patient  excreted  in  twenty-four  hours  1500  cu.  cm. 
of  urine  of  a  specific  gravity  of  1.035  ^"d,  rather  remarkably,  free  from  al- 
bumin. 

The  three  "  maux  perforants  "  had  made  terrible  ravages  in  the  foot,  which 
was  already  resected  through  Chopart's  joint ;  the  process  now  continued 
chiefly  along  the  tendons  of  the  peroneal  muscles.  Sensibility  was  distinctly 
diminished  on  this  leg,  and  there  was  a  distinct  retardation  of  the  perception 
of  needle-puncture.  There  being  no  indication  of  a  clot  in  the  popliteal  artery, 
I  proposed  amputation  below  the  knee,  which  was  effected,  with  an  excellent 
result  after  a  few  weeks  of  dietetic  and  restorative  treatment.  Nearly  three 
years  later  I  learned  that  the  patient  was  still  alive  and  in  possession  of  a 
good  stump. 

15.  E.,  fifty-four  years  old,  manager  of  a  factory,  ten  years  ago  sought 
life-insurance,  but  was  not  accepted  on  account  of  the  existence  of  glyco- 
suria.    The  history  gave  no  clue  to  the  origin  of  the  diabetes. 

The  patient  one  night  awoke  with  an  attack  of  serious  indisposition,  felt  a 
sensation  of  pressure  or  weight  in  the  occiput,  and  vomited  profusely.  The 
next  day  the  lower  branch  of  the  facial  and  the  abducens  nerve  on  the  right 
side  were  paralyzed.  The  patient  now  consulted  Dr.  Nordenson,  who  made 
the  following  note  :  "  In  both  eyes  numerous  small  hemorrhages  in  the  retina  ; 
around  the  macula  lutea  round  whitish  patches,  with  small  points  of  blood. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 49 

Field  of  vision,  normal  extent;  normal  color-perception.  Left  eye:  hyperme- 
tropia,  I  D. ;  visual  power,  0.3.  Right  eye:  hypermetropia,  1.50  D. ;  visual 
power,  0.3. 

Seven  weeks  later  ,the  patient  came  to  Carlsbad.  I  then  found  the  lower 
branch  of  the  right  facial  nerve  and  both  abducens  nerves  paralyzed — the 
right  eye  alone  seemed  to  be  used.  Other  symptoms  referable  to  the  nervous 
system,  besides  the  usual  neurasthenic  symptoms,  included  a  feeling  of  heavi- 
ness in  the  occiput  and  some  giddiness.  The  knee-jerk  was  absent  on  the 
left  and  barely  appreciable  on  the  right.  A  large  specimen  of  the  urine  con- 
tained about  three  per  cent,  of  glucose,  but  no  albumin  and  no  diacetic  acid. 
Eighty  grams  of  Graham  bread  and  some  green  vegetables  a  day  yielded  a 
urinary  secretion  of  from  2700  to  3000  cu.  cm.  a  day,  and,  quite  constantly, 
about  26  grams  of  glucose.  A  strict  diet  would,  beyond  a  doubt,  have  caused 
entire  disappearance  of  the  glucose.  With  the  use  of  syzygium  jambolanum 
on  three  different  occasions  the  glycosuria,  ceteris  paribus,  sank  to  15  grams, 
without  any  other  appreciable  change.  In  the  autumn  the  neuroparalytic 
symptoms  had  disappeared,  but  otherwise  the  state  of  the  eyes  had  undergone 
no  change. 

A  few  months  after  his  visit  to  Carlsbad  I  was  called  early  one  morning  to 
the  patient  in  Stockholm.  He  had  again  had  at  night  a  cerebral  attack  like 
the  previous  one.  After  a  rectal  injection,  application  of  an  ice-bag  to  the 
occiput  and  of  hot  bags  to  the  feet,  and  elevation  of  the  head,  the  attack  was 
soon  over  without  leaving  any  noteworthy  sequel. 

Half  a  year  later  gangrene  made  its  appearance  in  the  left  leg,  and  while 
the  patient  was  under  treatment  for  this  a  renewed  cerebral  attack  suddenly 
ended  his  life.  I  was  not  at  hand  and  there  was,  unfortunately,  no  postmortem 
examination. 

16.  E.  T.  B.,  a  farmer,  seventy-two  years  old,  was  considered  by  his  family 
and  friends  to  be  a  healthy  and  active  old  man.  Apart  from  his  eyes  he  had 
suffered  from  no  disease  whatever,  and  he  knew  of  no  reason  for  believing 
that  any  existed.  He  himself  and  others,  however,  were  struck  by  a  "  pecu- 
liarity "  that  had  made  its  appearance  about  thirty  years  previously — namely, 
that  he  drank  more  water  and  passed  a  greater  quantity  of  urine  than  other 
persons. 

The  patient  complained  that  his  eyes  had  for  many  years  been  a  source  of 
trouble,  and  stated  that  he  had  used  only  the  left  one.  Some  days  before 
coming  under  observation  this  eye  began  to  ache  ;  the  patient  obtained  from  a 
neighboring  physician  some  atropin,  which  made  the  eye  ache  "horribly." 
He  then  consulted  Dr.  Nordenson,  who  found  the  cause  of  the  "  peculiarity," 
and  sent  the  patient  to  me  on  account  of  his  diabetes. 

The  right  eye  presented  an  absolute  glaucoma.  The  upper  lid  was  some- 
what swollen,  the  conjunctiva  of  the  bulb  was  hyperemic,  and  there  was 
marked  pericorneal  injection.  The  cornea  was  smoky,  the  pupil  dilated,  and 
the  anterior  chamber  was  wanting.  The  vitreous  body  yielded  a  yellowish- 
brown  reflection  (hemorrhage). 

In  the  left  eye  there  was  found  hypermetropia  of  1.50  D,  with  a  visual  acuity 


I  50  DIABETES    MELLITUS    AND    GLYCOSURIA. 

of  0.8  ;  except  for  a  pronounced  gerontoxon,  the  cornea  was  normal.  The  iris 
also  was  normal  and  reacted  well.  At  the  bottom  of  the  eye  small  yellowish 
patches  could  be  seen  between  the  inferior  temporal  and  the  inferior  nasal 
vein.     A  considerable  hemorrhage  and  some  small  ecchymoses  were  visible. 

The  patient  did  not  complain  of  any  nervous  disorder  ;  the  sensibility  in  the 
left  leg,  however,  was  much  impaired.  The  knee-jerk  in  the  same  side  was 
almost  destroyed ;  the  toe-nails  were  discolored,  strongly  curved,  thick  and 
brittle ;  on  the  plantar  aspect  of  the  great  toe,  beneath  the  interphalangeal  joint, 
there  was  a  circular  scar  attached  to  the  bone  and  evidently  from  a  "  mal 
perforant,"  which  had  healed  a  couple  of  months  before,  under  treatment  by  a 
surgeon,  who,  by  the  way,  seemed  to  have  omitted  to  look  for  diabetes.] 

On  the  right  leg  there  was  no  "  mal  perforant,"  and  the  nervous  and  dys- 
trophic changes  were  much  less  marked  than  on  the  left  leg.* 

The  temporal  and  radial  arteries  were  somewhat  rigid,  pulse  104,  at  noon, 
before  lunch.  The  amount  of  urine  secreted  with  free  diet  was  2.5  liters,  with 
a  specific  gravity  of  1.046,  and  it  contained  eight  per  cent,  of  glucose. 

A  diet  including  an  abundance  of  green  vegetables,  about  100  grams  of  pota- 
toes, and  100  grams  of  rye-bread  yielded  1600  cu.  cm.  of  urine  containing  five 
per  cent,  of  glucose,  but  no  diacetic  acid.  It  is  probable  that  with  a  strict  diet 
the  urine  would  have  been  free  from^glucose. 

Three  years  later  the  patient  was  said  to  have  been  in  about  the  same 
state. 

17.  A  judge,  sixty-one  years  old,  nine  years  before  coming  under  observa- 
tion, after  some  loss  of  weight  and  a  sense  of  weakness,  was  discovered  to  be 
diabetic.  The  patient  himself  believed  the  dystrophy  to  be  due  to  exposure  to 
cold,  and  no  other  cause,  hereditary  or  acquired,  could  be  elicited.  During 
his  first  season  at  Carlsbad  the  patient  felt  fairly  well,  and  the  neurasthenic 
symptoms,  which  constituted  his  chief  complaint,  subsided  with  the  complete 
rest  of  his  sojourn  at  the  spa. 

The  power  of  assimilation  was  quite  good,  and  with  a  daily  allowance  of 
some  green  vegetables  and  150  grams  of  Graham  bread,  the  patient  passed 
1600  cu.  cm.  of  urine,  with  a  specific  gravity  of  1.025,  and  containing  only  faint 
traces  of  glucose. 

Two  years  later  the  patient  looked  much  less  well  and  complained  of  in- 
creasing weakness  and  incapability  of  fulfilling  his  public  duties.  Investiga- 
tion shows,  apart  from  the  results  of  urine  analysis,  only  one  important  change 
from  the  state  of  two  years  before — namely,  there  was  now  a  distinct  odor  of 
acetone  on  the  breath.  The  glycosuric  dystrophy  had  made  considerable  prog- 
ress, and  75  grams  of  Graham  bread  and  some  green  vegetables  yielded  1800 
cu.  cm.  of  urine  containing  1.3  per  cent,  of  glucose.  There  was  then  no  dis- 
tinct Gerhardt's  reaction.     The  patient,  who  seemed  entirely  reliable,  was  for  a 

*  About  the  same  time  Dr.  Kinnicutt,  of  New  York,  to  whom  I  mentioned  my  case, 
had  a  similar  one  under  observation,  with  marked  neuritis,  knee-jerk  almost  destroyed, 
"mal  perforant,"  and  other  dystrophic  changes  in  the  one  leg,  with  a  comparatively 
normal  state  in  the  other. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  I5I 

whole  week  put  on  strict  diet,  with  exclusion  of  carbohydrates.  He  then  lost 
weight  from  95.3  kilograms  to  93.4  kilograms,  and  the  urine  yielded  a  faint 
Gerhardt's  reaction  indicative  of  the  presence  of  diacetic  acid.  There  was  even 
now  about  o.i  per  cent,  of  glucose  in  the  urine  ;  this  could  scarcely  have  been 
derived  from  carbohydrates,  but  it  seemed  to  be  derived  partly  from  albumin. 
The  patient  undoubtedly  has  arrived  at  the  boundary  line  between  the  posi- 
tively mild  and  the  positively  severe  stage,  but  his  exact  place  can  not  be  deter- 
mined under  the  conditions  that  prevail  at  Carlsbad. 
Four  years  later  I  learned  that  the  man  was  still  alive. 

18.  A  merchant  first  became  my  patient  in  his  thirty-sixth  year.  His  father 
had  been  diabetic,  and  a  paternal  uncle  diabetic  and  insane.  Seven  years 
previously  the  patient  contracted  syphilis,  and  he  had  always  been  a  hard 
drinker.  Half  a  year  before  coming  under  observation  the  patient  observed 
that  white  spots  were  left  by  his  urine,  which  was  found  to  contain  six  per  cent, 
of  glucose  after  dinner.  Beyond  this  and  moderate  neurasthenia  the  man  was, 
during  his  first  season  in  Carlsbad,  fairly  healthy  and  quite  robust-looking. 
Thirty  grams  of  bread  and  some  green  vegetables  were  permitted  with  the 
food,  without  the  development  of  glycosuria.  As  the  patient  with  this  restric- 
tion maintained  his  weight  (92  kilograms)  the  diet  was  continued  for  five 
weeks. 

In  the  following  summer  the  condition  of  affairs  appeared  pretty  much  the 
same.  Sixty  grams  of  bread  and  some  green  vegetables  caused  a  trace  of  glu- 
cose to  appear  in  the  urine ;  the  bread  being  increased  to  90  grams,  the  nor- 
mal quantity  of  urine  for  twenty-four  hours  contained  fully  o.i  per  cent,  of 
glucose.  The  patient  had  entered  into  matrimonial  plans,  and  combated  ener- 
getically my  somewhat  feeble  opposition,  asserting  that  Providence  itself  was 
strongly  interested,  but  promised  moderation  in  all  respects. 

Two  years  later  the  man  again  appeared  in  Carlsbad,  having  carried  out 
his  plan  of  marrying,  but  having  entirely  forgotten  his  promise  of  moderation. 
Sixty  grams  of  bread  and  some  green  vegetables  now  yielded  1450  cu.  cm.  of 
urine  in  twenty-four  hours,  with  a  specific  gravity  of  1.032  and  containing  0.2 
per  cent,  of  glucose  and  no  diacetic  acid.  When  carbohydrates  were  entirely 
excluded  for  some  days  the  patient  lost  somewhat  in  weight,  while  the  glucose 
entirely  disappeared,  and  a  faint  Gerhardt's  reaction  developed  with  ferrichlo- 
rid.  As  the  drops  of  the  solution  fell  in  the  urine  they  were,  for  a  moment, 
surrounded  by  a  purple  zone,  the  urine  above  the  phosphates  having  the 
color  of  sherry.  In  the  following  year  the  power  of  assimilation  had 
again  decreased,  and  the  patient  was  in  the  severe  stage  of  the  dystrophy. 
Abstinence  from  carbohydrates  was  no  longer  followed  by  disappearance  of 
the  glycosuria,  though  only  a  few  grams  of  sugar  were  excreted  during  the 
twenty-four  hours.  Gerhardt's  reaction  was  now  well  pronounced.  About 
70  grams  of  bread  and  some  vegetables  yielded  1500  cu.  cm.  of  urine,  with  a 
specific  gravity  of  1.034  and  containing  rather  more  than  one  per  cent,  of  glu- 
cose. Upon  this  diet  the  patient  kept  his  weight,  but  a  distinct  though  faint 
Gerhardt's  reaction  could  still  be  elicited. 

Two  years  again  passed  and  the  patient  returned  to  Carlsbad.     The  bodily 


152  DIABETES    MELLITUS    AND    GLYCOSURIA. 

weight  was  almost  the  same  ;  the  glycosuric  dystrophy  had  again  made  some 
sHght  progress.  Mentally  the  patient  was  an  altered  man.  He  suffered  from 
melancholia,  without  stupor  or  hallucinations,  but  with  unfounded  ideas  of 
financial  ruin,  many  expressions  of  "  tedium  vitse  "  ;  terrible  anxiety  for  the 
future  mental  and  somatic  fate  of  a  new-born  son,  great  restlessness,  with  an 
occasional  "  raptus  "  during  the  nights,  and  general  profound  depression,  etc. 
The  "cure"  at  Carlsbad  somewhat  improved  the  man's  condition;  but 
during  the  autumn  the  melancholia  again  regained  its  sway  over  the  patient, 
who,  some  months  after  my  losing  sight  of  him,  was  found  lying  across  a  rail- 
way track  dead  and  mutilated. 

19.  H.,  a  clerk,  forty-six  years  old  when  I  saw  him  for  the  first  time  at 
Carlsbad,  had  known  for  two  years  that  he  was  diabetic,  but  distinct  polydipsia 
and  polyuria  had  been  present  for  five  years. 

A  history  was  obtained  only  with  the  greatest  difficulty,  owing  to  the  stu- 
pidity of  the  patient,  who  did  not  seem  to  know  anything  of  his  whole  past 
life,  except  that  he  had  acquired  syphilis  twenty-nine  years  before  and  had 
successively  passed  through  five  antisyphilitic  cures. 

The  man  was  extremely  peevish  and  irritable ;  he  slept  badly.  Sexual 
power  was  enfeebled.  Supraorbital  neuralgia  was  present  on  both  sides.  The 
teeth  were  partly  carious  and  partly  gone. 

The  urine,  which  had  lately  contained  so  much  as  seven  per  cent,  of  glu- 
cose, was  now  found  to  contain  three  per  cent.  There  was  no  odor  of  acetone 
on  the  breath,  no  diaceturia,  no  albuminuria.  A  restricted  diet  put  an  end  to 
the  glycosuria,  which  afterward  did  not  return  in  determinable  quantities  so 
long  as  the  patient  took  no  more  than  60  grams  of  white  bread  and  some  green 
vegetables. 

Ten  years  afterward  the  man  returned  to  Carlsbad.  His  breath  now  dis- 
tinctly smelled  of  acetone  ;  the  teeth  were  almost  all  gone  ;  the  tongue  showed 
longitudinal  and  transverse  furrows  "  a  la  crocodile.'"  Sexual  potency  was 
entirely  gone.  There  was  a  suspicion  of  neuritis  in  both  legs.  The  apex  of 
the  right  lung  exhibited  signs  of  tuberculosis,  and  in  one  place  there  was  a 
small  cavity.  The  pulse  was  84,  the  temperature  slightly  elevated.  The 
patient  complained  of  night-sweats. 

Exclusion  of  carbohydrates  for  several  days  reduced  the  glycosuria  to  0.6 
per  cent.,  1500  cu.  cm.  of  urine  with  a  specific  gravity  of  1.026  being  secreted 
in  twenty-four  hours ;  and  a  distinct  Gerhardt's  reaction  was  present.  Eighty 
grams  of  bread  and  100  grams  of  levulose  and  some  green  vegetables  with  the 
food  considerably  increased  the  glycosuria,  but  distinctly  diminished  the  diacet- 
uria (which,  however,  still  continued),  caused  some  restoration  of  weight  pre- 
viously lost,  and  maintained  the  bodily  weight  at  77  kilograms.  Syzygium 
jambulanum,  even  in  large  doses,  had  no  appreciable  effect. 

20.  Mrs.  L.,  thirty-eight  years  old,  knew  of  no  hereditary  or  other  etiologic 
causes  for  her  condition  than  an  excessive  fondness  for  sweets.  Her  diabetes, 
to  judge  from  the  polyuria  and  the  polydipsia,  had  probably  set  in  two  years 
before.  The  patient  was  extremely  stout,  and  did  not  lose  in  weight  until  her 
diet  was  restricted. 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  I  5  3 

During  her  first  season  in  Carlsbad  the  lady  appeared  in  fairly  good  general 
health.  There  was  no  smell  of  acetone  on  the  breath.  Some  teeth  were  carious, 
and  now  and  then  gingivitic  troubles  arose.  Some  of  the  usual  neurasthenic 
symptoms  were  present,  and  on  the  left  side  supraorbital  neuralgia  and  sciatica. 
Cramp  occurred  at  night  in  the  calves  of  the  legs.  There  was  a  tendency  to 
profuse  perspiration.  Finally,  the  patient  complained  of  pruritus  vulvs,  which 
speedily  ceased  on  application  of  a  solution  of  mercuric  chlorid  (i  :  looo)  twice 
a  day.  The  urine,  which  had  contained  four  per  cent,  of  glucose,  became 
normal  in  quantity  and  quality  upon  a  restricted  diet,  and  remained  so,  except 
for  small  traces  of  sugar  excreted,  when  60  grams  of  white  bread  and  some 
vegetables  were  added  to  the  dietary. 

Eleven  years  after  the  beginning  of  the  diabetes  the  patient  again  appeared 
in  Carlsbad  in  a  very  different  state.  She  had  diminished  in  weight  from  86 
to  67.15  kilograms  and  she  felt  very  weak.  The  skin  was  dry  and  of  cyanotic 
hue  upon  the  cheeks.  The  patient  was  no  longer  troubled  with  profuse  perspira- 
tion. The  breath  smelled  of  acetone  ;  the  teeth  were  defective  ;  the  tongue  was 
dry,  partly  coated,  and  of  an  angry  red  at  the  apex.  Restriction  of  diet  no 
longer  stopped  the  glycosuria.  The  weight  could  not  be  maintained  with  less 
than  100  grams  of  Graham  bread  and  some  vegetables  with  the  food,  upon 
which  the  patient  passed  2500  cu.  cm.  of  urine  containing  2  per  cent,  of  sugar 
and  with  a  distinct  (but  not  marked)  Gerhardt's  reaction,  but  no  albumin. 

A  year  later  small  ecchymoses  or  petechise,  sometimes  observed  in  advanced 
cases,  began  to  appear.  The  petechiae  disappeared  when  the  patient  remained 
in  bed,  and  reappeared  as  soon  as  she  moved  about.  They  were  present 
almost  exclusively  on  the  legs,  only  a  few  being  visible  on  the  trunk  and  none 
on  the  arms. 

Another  year  added  iritis  on  both  sides  and  cyclitis  on  the  left  side  to  the 
other  symptoms.  The  patient  was  then  in  an  advanced  cachectic  state,  and 
died  in  coma  a  few  weeks  after  the  appearance  of  the  ocular  symptoms. 

21.  Captain ,  forty-four  years  old,  an  officer  of  the  Guards,  had  in  the 

spring  received  from  his  physician  the  information  that  he  was  diabetic,  and  in 
August  he  came  to  Carlsbad. 

The  patient  had  during  the  preceding  months  at  home  felt  some  increased 
thirst  and  some  need  of  passing  his  urine  more  frequently  than  before ;  still, 
the  quantity  did  not  distinctly  exceed  the  normal  limits.  Apart  from  the  urine — 
which  at  the  time  of  the  patient's  arrival  contained  a  considerable  quantity  of 
glucose — there  were  scarcely  any  symptoms  at  all.  All  carbohydrates  were 
excluded  from  the  food,  and  during  a  week  of  strict  diet  the  patient's  weight 
went  down  from  86.7  kilograms  to  85.3  kilograms.  The  man  now  gradu- 
ally received  increased  amounts  of  carbohydrate.  The  urine  remained  nor- 
mal in  quantity  and  quality  until  more  than  90  grams  of  Graham  bread  and 
some  vegetables  were  given.  The  patient  had  a  splendid  appetite,  and  one 
day  passed  18  grams  of  nitrogen  with  his  urine.  When  120  grams  of  Graham 
bread  were  given,  the  mixed  urine  for  twenty-four  hours  contained  fully  o.i 
per  cent,  of  glucose.  The  patient  maintained  his  weight  and  felt  as  well  as 
ever. 

II 


154  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  next  year  the  man  again  appeared  at  Carlsbad,  on  May  7th,  His  gen- 
eral appearance  had  undergone  a  change  for  the  worse,  and  there  was  an  omi- 
nous smell  of  acetone  on  his  breath.  The  bodily  weight  had  fallen  to  83  kilo- 
grams. The  urine  contained  much  glucose,  and  yielded  a  distinct  though  not 
very  marked  Gerhardt's  reaction.  After  an  exclusion  for  five  days  of  carbo- 
hydrates the  patient  passed  2200  cu.  cm.  of  urine,  of  a  specific  gravity  of  1.018, 
with  0.5  per  cent,  of  glucose,  and  yielding  a  somewhat  more  pronounced  reac- 
tion with  the  solution  of  ferric  chlorid  than  at  the  patient's  arrival.  The 
patient  now  received,  daily,  a  large  piece  of  Seegen's  almond-bread,  which,  as 
it  is  sold  in  Carlsbad,  contains  a  not  inconsiderable  quantity  of  starch,  and  a 
generous  supply  of  fish,  meat,  butter,  and  eggs.  He  then  excreted  19.5  grams 
of  glucose  daily  and  Gerhardt's  reaction  was  less  pronounced,  though  distinct. 
He  still  lost  in  weight,  and  added  to  his  bill  of  fare  100  grams  of  levulose 
daily.  The  glucose  in  the  urine  increased  from  19.5  to  34  grams  in  the 
twenty-four  hours,  but  the  diaceturia  evidently  decreased  and  the  patient 
maintained  his  weight,  which  now  was  only  82.4  kilograms.  Some  ordinary 
bread  was  now  given,  and  the  bodily  weight  rose  to  83.3,  which  it  still  was 
when  patient  left  for  home,  after  a  stay  of  five  weeks.  There  had  constantly 
been  some  diaceturia. 

The  patient,  whom  I  asked  concerning  the  presence  of  fat  in  the  feces, 
was  able  to  detect  no  difference  from  the  ordinary  ^.ppearance. 

On  October  17th,  while  upon  a  fair  amount  of  carbohydrates  allowed  by  his 
physician  at  home,  the  man  expired  in  diabetic  coma.  No  autopsy  was  per- 
formed. 

This  case  represents  the  most  rapid  transition  from  a  distinctly  mild  to  a 
distinctly  severe  diabetes  that  I  have  ever  witnessed. 

22.  V.  X.,  thirty-five  years  old,  a  diplomatist,  belonged  to  a  family  that  has 
given  me  diabetic,  fatty,  and  gouty  patients.  The  man  had  been  a  hard 
smoker.  In  the  course  of  a  diplomatic  mission  to  Asia  he  had  to  stand  a  good 
deal  of  fatigue  and  of  emotion.  In  the  south  of  Europe  he  contracted  malaria. 
A  few  months  afterward  diabetes  suddenly  set  in,  and  took  the  patient  to 
Carlsbad  during  three  successive  seasons. 

The  man  was  exceedingly  sensitive  in  every  respect,  slept  badly,  and  a 
steep  declivity  made  him  giddy.  The  knee-jerks  were  present  and  moder- 
ately strong.  The  sexual  power  was  somewhat  weak,  although  the  patient 
begot  a  child  about  two  years  after  the  beginning  of  his  disease.  The  bodily 
weight  had  lately  kept  at  about  73  kilograms.  A  few  days  after  our  first 
acquaintance  he  invited  me  to  breakfast,  where  he  consumed  a  piece  of 
Graham  bread,  a  large  piece  of  butter  and  another  of  cheese,  one  partridge, 
two  sausages,  a  considerable  quantity  of  ham,  and  four  eggs.  We  often  after- 
ward took  meals  together,  and  I  always  found  him  with  an  enormous  appe- 
tite. 

The  teeth  grew  more  and  more  carious,  and  the  tongue  showed  more  and 
more  of  the  customary  appearance  in  severe  diabetes.  The  pulse  was  rarely 
below  100.     The  skin  was  dry  and  the  patient  was  often  troubled  by  itching. 

The  urine  after  a  few  days'  absolute  diet  contained  between  1.4  and  1.6  per 


SYMPTOMS    AND    COMPLICATIONS    OF    DIABETES.  1 55 

cent,  of  glucose  in  about  three  liters.  With  the  moderate  quantity  of  carbohy- 
drate necessary  for  the  maintenance  of  the  bodily  weight  and  of  a  fairly  good 
general  condition  it  increased  to  about  four  liters,  containing  between  2.6  and 
3  per  cent,  of  glucose.  During  the  whole  time  Gerhardt's  reaction  was  quite 
distinct,  and  the  urine  was  repeatedly  found  to  contain  some  /3-oxybutyric 
acid.     A  trace  of  albumin  was  always  present. 

When  the  patient  arrived  at  Carlsbad  for  the  third  time  there  was  no  oppor- 
tunity to  analyze  the  urine.  He  was  then  in  a  state  of  utter  exhaustion  ;  the 
frequent  pulse  and  the  dyspneic  respiration  already  foreboded  coma,  although 
they  were  to  some  extent  affected  by  a  left-sided  pneumonia.  The  patient 
was  seized  with  a  chill  on  the  cars.  A  flat  sound  on  percussion  was  elicited 
over  the  lower  part  of  the  upper  lobe  of  the  left  lung,  and  in  the  same  area 
distinct,  though  distant,  bronchial  respiration  was  audible.  Constipation  had 
been  present  for  four  days. 

A  large,  tepid,  rectal  injection,  with  the  addition  of  potassium  permanganate, 
whisky  and  enormous  doses  of  sodium  bicarbonate  by  the  mouth,  were  imme- 
diately given.  Coma  gradually  overwhelmed  the  patient,  the  specific  gravity 
of  the  urine,  which  from  the  beginning  of  his  disease  had  always  been  above 
1.035,  falling  to  1. 019,  and  the  glucose  to  1.3.  Gerhardt's  reaction,  which  had 
been  very  pronounced,  became  much  less  so  ;  still,  there  seemed  to  remain  some 
^-oxybutyric  acid  to  the  end.  There  was  some  expectoration  of  pneumonic 
sputa.     Death  took  place  six  days  after  the  patient's  arrival. 

On  postmortem  examination  a  central,  small  pneumonia  was  found  in  the 
left  lung.  The  pancreas  was  perhaps  somewhat  too  soft  in  consistency  and 
undersized  ;  otherwise  it  was  normal.  The  liver  was  in  a  state  of  pronounced 
fatty  degeneration.  The  spleen  was  hyperemic  and  about  twice  the  normal 
size.  The  kidneys  were  large,  hyperemic,  with  the  cortex  slightly  discolored 
by  fatty  degeneration. 

23.  Miss  B.,  a  teacher  of  music,  after  a  severe  attack  of  influenza  was  seized 
with  severe  diabetes. 

Her  general  health  failed  rapidly,  and  she  lost  quickly  in  weight,  in  spite 
of  an  enormous  appetite.     She  passed  daily  about  four  liters  of  urine. 

One  year  and  a  half  after  the  beginning  of  the  glycosuric  dystrophy  she 
came  to  Carlsbad  in  a  most  miserable  cachectic  and  marantic  condition. 
Eighty  grams  of  Graham  bread  and  some  vegetables  in  the  food  yielded  2000 
cu.  cm.  of  urine,  with  a  specific  gravity  of  1.037,  containing  4.4  per  cent,  of 
glucose  and  yielding  a  strongly  marked  Gerhardt's  reaction.  The  day  before 
coma  set  in  I  took  a  specimen  of  the  urine  and  found,  after  thorough  fermenta- 
tion and  precipitation  with  ammonia  and  lead  acetate,  the  ray  of  polarized  light 
deflected  to  the  left  between  0.4  and  0.5°  in  Hoppe-Seyler's  instrument. 

During  her  three  weeks'  stay  at  Carlsbad  a  most  wonderful  contrast  was 
evident  between  her  miserable  somatic  and  her  splendid  mental  state  ;  her 
courage  not  only  keeping  her  in  a  happy  frame  of  mind,  but  enabhng  her  con- 
stantly and  patiently  to  cheer  another  (most  intractable)  diabetic  lady.  I  had 
not  omitted  to  warn  her  of  the  danger  of  any  continued  constipation  ;  never- 
theless she  remained  in  such  a  state  for  four  days  without  taking  the  prescribed 


156  DIABETES    MELLITUS    AND    GLYCOSURIA. 

measures.  She  then,  during  a  walk  in  the  woods,  was  seized  with  the  pro- 
dromes of  coma,  and  was  brought  back  to  her  hotel,  where  I  immediately 
arrived.  The  brave  little  patient  presented  a  pulse  of  120  and  the  ominous 
"blowing"  respiration.  An  immediate  purging  injection  was  given;  she 
besides  received  whisky,  enormous  doses  of  sodium  bicarbonate  in  Geisshiibler 
water,  and  general  massage.  Being  able  to  take  no  solid  food,  the  patient 
drank  a  good  deal  of  levulose  in  Geisshiibler  water.  After  a  distinct  but  trans- 
itory improvement  the  coma  gradually  overpowered  the  patient,  and  after 
more  vigorous  clonic  convulsions  than  I  ever  saw  before  with  this  kind  of 
death,  the  girl  succumbed  on  the  third  day. 

24.  Augusta  J.,  forty  years  old,  a  widow  who  had  married  again,  grieved 
greatly  at  the  drunkenness  and  general  moral  degeneracy  of  her  second  hus- 
band, a  laborer,  and  was  suddenly  seized  with  symptoms  of  diabetes.  On 
October  29,  1891,  about  a  year  after  the  beginning  of  her  diabetes,  the  woman 
entered  Queen  Sophia's  Hospital,  in  Stockholm,  to  be  operated  on  for  cata- 
ract by  Dr.  Nordenson,  who,  previously  to  the  operation,  confided  her  to  my 
care  for  her  diabetes. 

The  patient  was  very  thin,  with  a  dry,  scaly  skin.  Her  tongue  was  thickly 
coated  at  its  base,  and  presented  the  customary  diabetic  type,  "  a  la  peau  croco- 
dile'' with  some  fleshy-looking  patches  and  an  atrophic  mucous  membrane. 
The  teeth  were  carious  and  the  breath  smelled  of  acetone. 

The  patient  suffered  from  continuous  headache  and  slept  badly.  There  was 
no  knee-jerk.  Hearing  was  poor;  vision,  which  was  excellent  a  year  before, 
was  destroyed  by  the  soft,  diabetic  cataract.  At  the  apex  of  the  right  lung  there 
was  in  a  small  area  a  somewhat  sharp  respiratory  sound  and  a  higher-pitched 
percussion-note.     The  pulse  was  100. 

The  headache  might  have  been  a  precursory  sign  of  coma  ;  but  it  had  lasted 
for  a  whole  year,  and  could  be  more  easily  explained  in  almost  any  other  way. 
The  urine, — which  with  an  almost  free  diet  amounted  to  about  three  liters,  of 
high  specific  gravity,  and  contained  six  per  cent,  of  glucose  and  a  trace  of 
albumin, — after  fermentation  of  the  glucose  and  precipitation  of  the  combined 
glycuronic  acids  with  lead  acetate  and  ammonia,  deflected  the  ray  of  polarized 
light  to  the  left  only  slightly  (0.2°  with  Hoppe-Seyler's  instrument),  and 
yielded  a  moderately  pronounced  Gerhardt's  reaction.  On  account  of  the 
presence  of  but  a  small  amount  of  /3-oxybutyric  acid,  I  considered  it  not 
dangerous  for  three  days  to  exclude  carbohydrates  from  the  food.  The  patient 
received  an  abundant  food  in  eggs,  fish,  different  meats,  and  butter — a  seem- 
ingly much  better  diet  than  her  poor  fare  at  home,  chiefly  consisting  of  herring 
and  potatoes.  After  three  days,  when  I  had  found  out  how  much  glucose  was 
being  excreted  with  the  strict  diet,  the  patient  was  to  receive  60  grams  of  white 
bread  and  a  considerable  amount  of  vegetables  every  day. 

Polyuria  and  glycosuria  quickly  diminished,  but  Gerhardt's  reaction  became 
much  more  marked,  even  comparatively,  and  during  the  night  of  November 
2d-3d  violent  diarrhea  began.  When  I  visited  the  patient  on  the  morning 
of  November  3d,  coma  evidently  was  threatening.  Respiration  was  blowing 
and  dyspneic,  the  pulse  120,  the  temperature  in  the  rectum  35°  C.  (95°  F.)  in 


DIABETES    INFANTILIS.  I  5/ 

the  morning  and  34.4°  C.  (93.9°  F.)  in  the  afternoon.  The  patient  was  given 
brandy  in  strong  tea,  together  with  eggs,  biscuits,  and  enormous  quantities  of 
sodium  bicarbonate  water.  When  she  could  eat  no  biscuits,  and  no  levulose 
could  be  had,  I  gave  her  cane-sugar  in  my  anxiety  to  increase  the  carbo- 
hydrates. Marked  improvement  followed,  and  when  the  danger  of  coma 
seemed  much  diminished,  some  opium  was  given  for  the  diarrhea.  The 
patient  improved  greatly.  On  November  7th  the  pulse  was  84,  the  temperature 
36.8°  C.  (98°  F.),  respiration  almost  normal,  the  sensorium  and  intelligence 
seemed  quite  free,  and  I  began  to  hope  that  I  should  escape  too  severe  con- 
sequences of  this  ill-timed  dietetic  system,  still  defended  by  powerful 
authorities.  Diarrhea,  however,  again  began  on  November  8th,  and  the 
patient  became  more  and  more  comatose,  and  died  on  November  i6th.  Dur- 
ing the  period  of  coma  the  glucose  sank  to  0.7  per  cent.,  the  urea  to  0.35  per 
cent.,  the  chlorids  likewise  to  a  minimum,  and  the  specific  gravity  to  1.013. 
The  phosphoric  acid  decreased  less,  and  was  o.i  per  cent.  The  temperature, 
which  before  had  constantly  been  somewhat  below  the  normal,  during  the  last 
days  went  up  to  38°  C.  (100°  F.)  in  consequence  of  the  pulmonary  lesion. 

On  postmortem  examination  the  muscles  were  found  dry  and  atrophic,  the 
dura  somewhat  thickened,  the  pia  distended  with  edema,  the  heart  small, 
pale,  and  flabby,  while  the  right  lung  contained  a  caseous  focus.  The  liver 
was  partly  in  a  state  of  fatty  degeneration  and  partly  exhibited  rose-red  spots 
and  an  appearance  suggestive  of  the  nutmeg-liver.  The  pancreas  was  in 
every  respect  normal.  The  kidneys  were  large,  flabby,  pale,  with  the  cortex 
somewhat  discolored.  The  spleen  was  normal.  A  strong  smell  of  acetone 
filled  the  room. 


CHAPTER  V— DIABETES  INFANTILIS.^ 

The  pathologic  excretion  of  glucose  is  much  rarer  in  children 
than  in  adults,  and  almost  always  represents  either  a  simple,  trans- 
itory glycosuria  from  some  accidental  cause,  or  a  severe  diabetes, 
which  may  lead  to  death  in  the  course  of  a  few  weeks,  and  hardly 
ever  fails  to  do  so  in  the  course  of  a  few  years.  Still,  in  excep- 
tional cases  it  happens  that  a  child  suffers  from  protracted  dia- 
betes in  the  mild  stage. 

*  Niedergesass  (1873),   Redon  (1877),  Kiilz  (1878),  Leroux  (1880),   Stern  (i 
and  others  have  written  on  Diabetes  infantilis. 


158  DIABETES    MELLITUS   AND    GLYCOSURIA. 

Simple  glycosuria  in  children  generally  occurs  in  conjunction 
with  neuroses  and  with  the  infectious  fevers,  but  it  may  arise  from 
any  cause  that  has  the  same  effect  in  adults.  It  has  been  observed 
by  a  number  of  clinicians  in  cases  of  diphtheria,  scarlet  fever,  and 
measles,  and  also  in  cases  of  epilepsy,  chorea,  supraorbital  neuralgia 
(Franque,  Goolden,  and  others).  In  cases  of  pertussis  and  croup 
it  may  be  the  result  of  asphyxia  (Laborde).  Lecoq  mentions  the 
appearance  of  from  o.i  to  0.2  per  cent,  of  glucose  in  the  urine  of 
healthy  children  who  had  eaten  sweets  (?  ?).  Parrot  found  glucose 
in  more  than  one-third  of  all  athreptic  children,  especially  in  those 
that  were  cyanotic.  I  have  several  times  found  distinct  traces  of 
glucose  in  boys  that  had  been  addicted  to  masturbation.  I  believe 
that  in  many  such  cases  true  diabetes  may  develop  in  middle  age, 
though  one  may  see  glycosuria  disappear  in  other  cases.  Pro- 
tracted glycosuria  is  much  rarer,  and  is  of  much  greater  significance 
in  children  than  in  adults.* 

True  diabetes  is  so  rare  in  early  childhood  that  many  an  expe- 
rienced children's  physician  and  many  a  specialist  in  diabetes  have 
never  seen  a  diabetic  patient  under  ten  years  of  age.  Romberg 
observed  among  5900  infant  patients  but  a  single  case  of  diabetes. 
Schmitz  encountered  among  21 15  cases  of  diabetes  10  patients  in 
the  first  and  75  patients  in  the  second  decad  of  life. 

Prout  saw  among  700  cases  of  diabetes  one  child  under  five 
years  old.f  It  is  only  by  mere  accident  that  in  the  course  of  little 
more  than  a  year  (1895- 1896)  I  have  been  consulted  in  four  cases 
of  diabetes  in  children  under  ten  years  of  age,  while  previously  I 
had  seen  but  a  single  such  case.  On  the  other  hand,  I  have  seen 
a  not  inconsiderable  number  of  cases  in  children  between   ten  and 


*  Cantani  urges  the  necessity  of  looking  for  glucose  in  cases  of  nocturnal  enuresis. 
If  one  does  so,  and  in  the  presence  of  a  reducing-substance  verifies  it  as  glucose  by  the 
fermentation-test,  he  will  find  that  in  the  great  majority  of  the  common  cases  of  nocturnal 
enuresis  the  urine  is  free  from  glucose. 

f  I  have,  unfortunately,  taken  notes  of  my  diabetic  cases  only  during  recent  years, 
and  do  not  know  their  number  ;  but  my  5  cases  of  diabetes  in  children  under  ten  years 
occurred — one  in  a  girl  six  years  old,  in  the  central  part  of  Sweden  ;  another  in  a  girl  four 
years  old,  in  Stockholm  ;  2  boys  of  four  and  of  nine  years,  respectively,  in  Stockholm; 
and  one  boy  of  four  years,  in  New  York.  For  two  of  my  cases  in  Stockholm  and  for 
the  case  in  New  York  I  am  indebted  to  my  esteemed  friends.  Dr.  Nettelbladt  and  Dr. 
Kinnicutt,  respectively. 


DIABETES    INFANTILIS.  I  59 

fifteen,  and  some  in  girls  and  boys  between  fifteen  and  twenty  years 
old.  Statistics  show  that  the  third  quinquennium  of  life, — viz.,  from 
ten  to  fifteen  years, — of  the  first  four  quinquenniums  is  that  in  which 
diabetes  occurs  most  frequently.  In  the  period  from  fifteen  to 
twenty  years  diabetes  again  becomes  rarer,  while  from  the  latter 
age  it  continues  to  grow  more  frequent. 

It  is  of  great  interest  to  see  how  the  total  frequency  increases,  and  how  the 
greater  frequency  among  boys  than  among  girls  shows  itself  from  the  second 
decad,  in  which  both  sexes  begin  to  be  somewhat  strained  intellectually,  and 
in  which,  unfortunately,  sexual  excesses  (masturbation)  among  boys  already 
begin  to  become  frequent.  Among  136  cases  of  diabetes  up  to  the  age  of  fifteen 
years,  there  were  27  cases  during  the  first,  32  during  the  second,  and  ']']  during 
the  third  quinquennium  of  life  (Leroux).  Pavy  has  observed  5  girls  and  3  boys 
in  the  first,  and  35  boys  and  22  girls  in  the  second  decad  of  life. 

In  children  under  ten  the  relative  frequency  in  the  two  sexes  differs  from 
the  analogous  figures  later  in  life.  In  adults  the  ratio  between  diabetic  men 
and  diabetic  women  is  best  represented  by  the  figures  3:1.  But  among  dia- 
betic children  under  ten  years  of  age  we  find  at  least  as  many  girls  as  boys. 
Among  102  cases  at  this  period  there  were  57  girls  and  45  boys.  Leroux  alone 
has  observed  what  he  calls  a  " statistique  favorable  aux gargons''  :  namely,  22 
boys  and  16  girls.  Kiilz's  and  Leroux's  figures  from  different  sources  and  my 
own  5  cases  make  up  the  usual  small  majority  for  the  girls  in  early  childhood  : 
75  girls  and  70  boys. 

The  causes  are,  of  course,  the  same  for  children  as  for  adults, 
but  there  is  some  difference  in  their  relative  efficiency.  Hereditary 
influence  is  exceedingly  important  in  childhood.  Isenflamm,  as 
early  as  1784,  mentions  an  instance  of  diabetes  in  7  brothers,  who 
all  died  at  the  age  of  seven  or  eight  years.  Roberts  observed  8 
diabetic  children  in  the  same  family ;  Watson,  Bence -Jones,  and 
West  each  saw  3  ;  and  in  India  such  cases  are  common.  I  am  in- 
clined to  believe  that  infectious  diseases  are  the  most  frequent  acci- 
dental cause  of  diabetes  in  children  ;  in  adults  emotions  and  mental 
sufferings  play  a  much  more  important  role.  Trauma  is  the  cause 
of  a  greater  percentage  of  infantile  than  of  other  cases.  Finally, 
both  from  reports  in  literature  and  from  two  of  my  own  cases,  I  am 
inclined  to  believe  that  starvation  is  a  relatively  more  frequent  cause 
in  childhood  than  later  in  life  (Andral,  Heine,  Senator,  Ingerslev, 
and  others  have  seen  such  cases). 

Infantile  diabetes  usually  is  like  the  worst  cases  in  adults,  and 
presents    itself   as   a  terrible  dystrophy  with  a  rapid    course.      It 


l60  DIABETES    MELLITUS    AND    GLYCOSURIA. 

is  especially  in  these  cases  that  one  sometimes  hears  the  date  of 
the  attack  named.  "  The  20th  of  April  my  boy  was  in  perfect 
health  ;  the  21st  he  was  very  ill,  and  drank  as  much  as  he  could 
the  whole  day,"  the  father  of  a  four-year-old  diabetic  boy  told 
me  some  time  ago.  The  little  victims  suddenly  stop  playing  and 
become  quiet  and  drowsy,  irritable  and  peevish.  The  diabetic 
symptoms  rapidly  reach  a  maximum  of  intensity.  There  are  on 
record  reports  of  cases  in  which  sixteen  liters  of  urine  and  one  kilo- 
gram of  glucose  were  secreted  in  the  twenty-four  hours.  The 
urine  usually  is  pale,  greenish-yellow  in  color,  and  of  high  specific 
gravity.  In  a  case  seen  by  Redon  the  latter  was  1.070.  Ger- 
hardt's  reaction  is  often  distinct  from  the  beginning.  In  a  few 
months  the  cavity  of  the  mouth  may  present  a  furrowed  tongue, 
partly  with  a  thick,  brownish  covering,  partly  with  fleshy,  flayed- 
looking  patches,  and  carious  teeth  ;  it  often  becomes  the  seat  of  a 
luxuriant  vegetation  of  Oidium  albicans.  The  soft,  diabetic  cataract 
may  develop  in  an  amazingly  short  time,  and  at  quite  an  early  age. 
In  one  of  my  cases,  to  be  related  later,  the  patient  was  fourteen 
years  old.  The  face  is  either  pale  or  it  may  present  a  circumscribed, 
cyanotic,  red  discoloration  on  the  cheeks  ;  the  skin  is  dry  and 
squamous.  Girls  suffer  from  vulvitis,  boys  from  phimosis  and  balano- 
posthitis.  The  loss  of  flesh  can  not  be  checked,  and  the  children 
become  exceedingly  weak  and  have  to  keep  their  beds.  The  tem- 
perature, apart  from  febrile  complications,  keeps  below  the  nor- 
mal, but  even  in  these  cases  rarely  below  36°  C.  (96.8°  F.). 

The  prognosis  is  extremely  bad,  and  I  do  not  know  that  in  any 
of  the  typical  infantile  cases  the  patient  has  returned  to  health.* 

In  cases  of  diabetes  in  the  first  decad  of  life  death  often  takes 
place  within  a  year  ;  a  longer  duration  than  two  years  after  the 
first  appearance  of  symptoms  at  this  age  is  rare,  and  the  rarer,  the 
younger  the  patient.     In  some  cases  the  dystrophy  leads  to  death 


*  There  are  many  reports  of  complete  recovery  even  from  infantile  diabetes.  Of  96 
cases  from  11  different  writers  I  find  8;^  with  a  fatal  issue  and  13  in  which  recovery 
ensued.  These  reports  are  as  unreliable  as  the  analogous  ones  concerning  adult  cases. 
But  as  in  cases  of  diabetes  from  infections  and  from  trauma  the  prognosis  is  better  than 
in  other  cases,  and  as  these  causes  are  relatively  frequent  in  infantile  cases,  I  presume 
that  true  diabetes  in  a  child — which  may  be  a  mild  diabetes — now  and  then  has  dis- 
appeared. 


DIABETES    INFANTILIS.  l6l 

in  a  few  weeks.     The  fatal  issue  in  most  cases  is  brought  about  by 
coma  or  marasmus.* 

As  infantile  cases  are  comparatively  rare,  I  record  here  one  of  my  own  from 
each  of  the  four  first  quinquenniums. 

Ellen  W.,  four  years  old,  had  an  insane  aunt.  The  father  is  very  "  reli- 
gious." On  December  i6th  I  was  called  to  see  the  child,  and  on  asking  about 
the  duration  of  the  disease  the  mother  answered  :  "  She  fell  ill  the  5th  of 
November." 

The  girl  was  pale  and  almost  only  "  skin  and  bones."  The  tongue  already 
presented  the  diabetic  type,  the  teeth  were  carious,  and  the  breath  smelled  of 
acetone.  Thrush  reappeared  in  several  places  constantly  as  quickly  as  it  was 
got  rid  of.  The  child  was  irritable,  but  otherwise  drowsy  ;  a  certain  degree  of 
poisoning  was  already  manifest.  The  reflexes  were  extinguished.  Severe 
epigastric  pain  caused  the  patient  to  cry  out  with  anguish.  The  pulse  was  80, 
the  temperature  in  the  rectum  36.2°  C.  (97.2°  F.). 

The  child  received  about  75  grams  of  bread  with  her  food.  The  urine  ex- 
creted amounted  to  2500  cu.  cm.,  had  a  specific  gravity  of  1.040,  and  yielded  a 
pronounced  Gerhardt's  reaction,  some  /3-oxybutyric  acid,  and  a  large  quantity  of 
glucose.  The  introduction  of  this  allowance  of  carbohydrate  after  the  previous 
strong  restriction  was  followed  by  decided  improvement;  coma,  however,  was 
only  put  off  for  four  weeks.     No  postmortem  examination  was  held. 

B.,  a  boy  nine  years  old,  had  a  "  nervous  "  mother,  two  insane  aunts,  and 
an  uncle  who  died  by  suicide.  (There  are,  however,  reasons  for  suspecting  the 
boy's  diabetes  to  be  of  pancreatic  origin.     See  below.) 

About  a  year  before  the  child  came  under  my  observation  he  began  to  wet 
his  bed,  and  the  family  physician  found  an  abundant  quantity  of  glucose  in  the 
urine. 

When  I  saw  the  boy  on  April  i,  1896,  he  was  in  an  exceedingly  miserable 
state.  His  appetite  was  voracious.  He  had,  however,  lost  a  great  deal  of 
weight,  and  the  outlines  of  the  wasted  muscles  were  distinctly  to  be  seen 
through  the  dry,  atrophic  skin.  The  mental  state  had  lately  gone  from  bad  to 
worse,  and  the  boy,  who  had  previously  been  of  a  gentle  disposition  and  of 
quite  excellent  parts,  was  now  usually  apathetic,  but  on  the  slightest  provoca- 
tion was  subject  to  attacks  of  violent  rage,  followed  by  deep  depression.  Sleep 
rarely  came  before  three  in  the  morning.  After  exertions  attacks  of  general 
clonic  spasms  occurred,  with  full  consciousness.  A  continuous  headache  exacer- 

*  In  21  cases  collected  by  Redon  from  different  writers  there  were  9  deaths  from 
marasmus  without  coma,  3  from  marasmus  with  coma,  4  from  pulmonary  tuberculosis,  3 
from  acute  inflammation  of  the  lungs,  and  2  from  cerebral  affections.  Concerning  these 
statistics,  it  may  be  remarked  that  the  number  of  deaths  attnbuted  to  coma  is  doubtless 
much  too  small ;  coma  seems  to  be  the  most  frequent  mode  of  death  in  cases  of  infantile 
as  well  as  those  of  other  severe  forms  of  diabetes. 


1 62  DIABETES    MELLITUS    AND    GLYCOSURIA, 

bated  in  the  morning  and  in  the  evening.  Sciatica  was  present  on  both  sides. 
The  knee-jerk  was  slight  on  the  left,  but  almost  normal  on  the  right  side.  On 
the  left  leg  sensibility  was  distinctly  diminished.  Psoriasis  was  present  on  both 
knees.  Vision  was  normal.  The  pulse  was  66,  the  temperature  in  the  rectum 
37.3°  C.  (99°  F.).  Later,  the  patient's  mental  state  did  not  permit  thorough 
examination. 

The  feces  consisted  partly  of  white-colored  fatty  masses.  (Were  it  not  for 
this  symptom,  one  might  be  inclined,  on  account  of  the  strong  neurotic  in- 
heritance, to  consider  the  case  one  of  neurogenic  diabetes.) 

After  considerable  though  not  absolute  restriction  of  carbohydrates  a  large 
sample  of  urine  was  found  to  have  a  specific  gravity  of  1.038  and  to  contain 
6.6  per  cent,  of  glucose,  some  diacetic  acid,  but  not  an  appreciable  amount  of 
j8-oxybutyric  acid.  The  disease,  which  probably  for  some  time  had  kept  within 
the  light  stage,  had  lately,  according  to  a  chemist's  calculation,  caused  a  loss  of 
nearly  one  kilogram  of  glucose  a  day.  The  maximum  measured  quantity  of 
urine  in  my  observation,  however,  did  not  exceed  eight  liters. 

The  boy  had  previously  lived  on  a  more  or  less  rigid  diet,  but  on  account  of 
his  despair  with  regard  to  his  food  some  concessions  had  lately  been  made. 
The  state  was  such  that  none  of  the  three  physicians  who  saw  him  believed 
that  his  life  would  be  spared  for  more  than  a  few  weeks.  The  treatment  now 
was  directed  chiefly  against  the  nervous  symptoms.  The  diet  was  changed, 
and  the  patient  was  allowed  to  eat  as  much  bread  as  he  wished,  and  green  vege- 
tables and  levulose  were  added  to  his  bill  of  fare.  The  polyuria  and  the  poly- 
dipsia, of  course,  increased  at  once,  but  the  mental  and  general  state  improved 
manifestly,  and  the  hitherto  continuous  loss  of  flesh  stopped.  To  our  amaze- 
ment the  patient  lived  not  only  through  the  whole  of  1896,  but  also  through 
the  greater  part  of  1897,  and  died  in  October  of  that  year,  not  from  coma  or 
marasmus,  but  from  a  carbuncle  on  the  head.  I  did  not  dare  to  ask  for  a  post- 
mortem examination. 

It  is  my  firm  opinion  that  any  considerable  restriction  of  carbohydrates 
would  have  led  to  a  much  earlier  death,  though  I  fully  acknowledge  the  small 
value  of  the  patient's  last  year  for  himself  and  others. 

Anna  Charlotta  J.,  fourteen  years  old,  did  not  know  much  about  her  family, 
but  described  the  evident  epilepsy  of  her  sister. 

At  the  age  of  twelve  the  girl  lived  for  two  months  as  a  servant  with  some 
poor  people,  and  literally  starved.  When  she  again  returned  to  the  compara- 
tively good  table  of  her  home,  she  became  diabetic. 

Somewhat  more  than  two  years  afterward  the  child  was  admitted  to  Queen 
Sophia's  Hospital  in  Stockholm  to  be  operated  upon  for  typical,  diabetic,  soft 
cataract  on  both  eyes  (Nordenson).  I  found  her  very  thin,  pale,  and  anemic, 
with  a  dry,  scaly  skin.  She  was  moderately  depressed,  somewhat  irritable, 
slept  fairly  well,  had  normal  knee-jerks,  and  felt  "  creepings  "  in  the  arms  and 
legs.  The  teeth,  though  still  fairly  good,  now  began  to  be  carious,  and  the 
tongue  was  dry  and  of  a  vivid  red,  while  fissures  formed  in  both  angles  of  the 
mouth.  The  appetite  was  voracious.  The  liver  was  normal  in  size,  consis- 
tency, and  sensibility.     The  bowels  were  somewhat  sluggish. 


DIABETES    INFANTILIS.  I  63 

Over  the  apex  of  the  right  lung  in  one  place  there  was  some  flatness  of  the 
percussion-note. 

The  pulse  was  120  in  the  morning.  The  temperature  was  somewhat  below 
the  normal  during  the  whole  time.     The  weight  was  28!kilograms. 

A  sample  of  urine  obtained  when  the  patient,  who  had  eaten  whatever  she 
wanted,  arrived  had  a  specific  gravity  of  1.046,  contained  9.2  per  cent,  of  glu- 
cose, was  free  from  albumin,  and  yielded  a  dark  bluish-purple  reaction  with 
ferric  chlorid. 

During  the  first  days  the  patient  received  90  grams,  and  afterward  60  grams, 
of  rye-bread,  some  green  vegetables,  and  four  glasses  of  unskimmed  milk  a 
day,  with  much  butter,  meat,  fish,  and  eggs. 

The  bodily  weight  increased  from  28  kilograms  on  December  ist  to  30 
kilograms  on  December  23d.  Then  dyspeptic  troubles  arose,  with  diarrhea 
and  a  loss  of  weight  in  one  week  of  nearly  two  kilograms.  Opium  was  given 
and  the  patient  was  allowed  80  grams  of  white  bread  daily. 

By  January  5th  -the  girl  had  regained  her  bodily  weight  and  reached  her 
maximum  of  30.3  kilograms.  The  general  state  also  was  at  its  best.  The 
daily  portion  of  bread  was  again  reduced  to  60  grams.  With  this  diet  the 
urine  amounted  to  from  2  to  2.5  liters  and  contained  upward  of  5  per  cent,  of 
glucose.  Gerhardt's  reaction  constantly  was  pronounced,  as  manifested  by  a 
rich  Burgundy  color;  after  fermentation  and  precipitation  with  ammonia  and 
lead  acetate  the  urine  still  deflected  the  ray  of  polarized  light  in  Hoppe-Seyler's 
instrument  about  0.2  degrees  to  the  left  (/3-oxybutyric  acid).  The  urine  from 
8  P.  M.  to  8  A.  M.  generally  was  a  little  more  abundant  than  the  urine  collected 
during  the  day,  but  not  rarely  the  contrary  happened. 

On  January  7th  the  urine  for  twenty-four  hours  amounted  to  2125  cu.  cm., 
and  had  a  specific  gravity  of  1.034,  with  4.4  per  cent,  of  glucose.  It  yielded, 
as  usual,  a  marked  Gerhardt's  reaction,  and,  for  the  first  time,  contained  a 
small  quantity  of  albumin. 

On  January  loth  the  patient  presented  the  well-known  prodromes  of  coma. 
She  had  been  very  uneasy  during  the  night,  and  was  then  in  terrible  anguish, 
but  intelligence  and  sensorium  were  still  clear.  The  patient  complained,  at 
times  with  loud  cries,  of  violent  epigastric  pains.  The  pulse  was  nearly  150, 
the  respiration  28.  The  girl  was  given  tea  with  brandy,  liquor  ammoniac, 
anisatus,  a  rectal  injection  of  tepid  water,  a  warm  bath  (39°  C.)  (102.2°  F.),  and 
general  massage.  The  diet  was  unrestricted,  and  enormous  quantities  of 
sodium  bicarbonate  were  given  in  soda-water.  After  a  marked  but  transitory 
improvement  the  patient  struggled  on,  with  shght  changes,  until  the  12th,  when 
drowsiness  became  manifest.  The  epigastric  pains  had  now  stopped,  the  res- 
piration was  25,  the  pulse  132 ;  the  2125  cu.  cm.  of  urine  had  a  specific  gravity 
of  only  1. 021,  with  2.7  per  cent,  of  sugar  and  some  diacetic  acid.  On  January 
13th  the  specific  gravity  was  i.oig  and  the  glucose  1.2  per  cent.  The  patient 
remained  conscious  until  noon,  with  only  slightly  impaired  intelligence,  but 
then  became  comatose  and  died  quietly  at  7  A.  M. 

Upon  postmortem  examination  the  dura  mater  was  found  somewhat  thick- 
ened, the  pia  distended  by  an  abundant  edema.  The  fourth  ventricle  and  the 
aqueduct  of  Sylvius   and  adjacent  parts  seemed   to   the  naked  eye  normal. 


164  DIABETES    MELLITUS    AND    GLYCOSURIA. 

beyond  some  perivascular  spaces,  such  as  Dickinson  has  described.  A  large 
part  of  the  sympathetic  nerves  was  carefully  dissected,  and  seemed  perfectly 
normal.  The  heart  was  pale  and  small.  At  the  apex  of  the  right  lung  was  a 
caseous  nucleus  of  the  size  of  a  pea.  The  pancreas  was  normal.  The  liver 
was  somewhat  hyperemic.  The  mesenteric  glands  were  enlarged  ;  one  of  them 
was  caseous.     The  kidneys  were  large  and  hyperemic. 

Miss  G.  v.,  nineteen  years  old.  with  a  maternal  neurotic  inheritance,  began 
to  feel  exceedingly  thirsty  in  November,  and  consulted  me  January  28th. 

There  was  polydipsia,  polyuria,  and  pollakiuria.  The  formerly  gentle  dis- 
position of  the  patient  was  changed  into  one  of  great  irritability.  Sleep  was 
bad,  and  there  was  constant  headache.  The  knee-jerks  were  very  weak. 
The  teeth  were  partly  carious,  partly  absent.  The  gingiva  around  a  molar 
tooth  was  swollen,  and  an  incision  was  followed  by  the  escape  of  a  drop  of 
pus ;  a  probe  passed  rather  deep  along  the  root  of  the  tooth.  The  tongue 
was  coated,  and  with  a  dry,  bright-red  apex.  A  strong  smell  of  acetone  was 
present  on  the  breath. 

The  patient  was  exceedingly  anemic,  and  over  the  jugular  vein  a  pronounced 
"  bruit  du  diable  "  was  audible.  The  apex  of  the  right  lung  was  slightly 
infiltrated. 

A  specimen  of  urine  had  a  specific  gravity  of  1.040,  with  8.2  per  cent,  of 
glucose,  a  marked  Gerhardt's  reaction,  and  a  small  quantity  of  ;8-oxybutyric 
acid. 

Sixty  grams  of  white  bread  and  some  green  vegetables  in  the  food  yielded 
about  170  grams  of  glucose  a  day  in  3000  cu.  cm.  of  urine. 

At  the  end  of  May  the  patient  died  in  diabetic  coma. 


CHAPTER  VI.— DIABETES  MELLITUS  FOLLOWING   EXTIR- 
PATION OF  THE  PANCREAS. 

As  I  have  mentioned,  a  connection  between  lesions  of  the  pan- 
creas and  the  glycosuric  dystrophy  had  long  been  suspected  by 
many  and  accepted  by  some.  Finally,  in  1889,  v.  Mering  and 
Minkowski  communicated  to  the  Association  for  Natural  Sciences 
of  Strasburg  their  great  discovery  that  total  extirpation  of  the  pan- 
creas gives  rise  to  severe  diabetes,  characterized  by  glycosuria 
under  all  dietetic  conditions,  polydipsia  and  polyuria,  rapid  loss  of 
weight,  the  presence  of  acetone,  diacetic  acid,  /3-oxybutyric  acid. 


DIABETES    MELLITUS    AFTER    REMOVAL    OF    PANCREAS.  165 

and  an  increased  amount  of  ammonia  in  the  urine,  and  death  in 
diabetic  coma.  These  admirable  and  successful  investigators  had 
discovered  the  only  certain  method  yet  known  of  producing  "  arti- 
ficially" true  severe  diabetes.  They  had,  further,  studied  this  form 
of  diabetes  conscientiously.  Minkowski  afterward  continued  the 
researches  in  a  careful  and  extensive  scientific  investigation.  About 
the  same  time  De  Dominicis,  in  Italy,  independently  of  others,  also 
observed  (in  dogs)  diabetes  after  extirpation  of  the  pancreas. 

Later,  Aldehoff,  Sandmeyer,  Lepine,  Hedon,  Gley,  Thiroloix, 
Chauveau  and  Kaufmann,  Gaglio,  Caparelli,  and  others  made  re- 
searches on  diabetes  after  extirpation  of  the  pancreas.  Unfortu- 
nately, these  researches  have  on  many  points  led  to  such  different 
results  that  definite  conclusions  are  at  present  impossible,  though,  on 
the  other  hand,  many  important  facts  have  been  added  to  our  stock 
of  knowledge. 

Diabetes  mellitus  following  extirpation  of  the  pancreas  has  been 
observed  in  dogs,  cats,  and  hogs  (v.  Mering  and  Minkowski), 
hawks  (Langendorf),  falcons  (Weintraud),  geese  (Kausch),  turtles 
and  frogs  (Aldehoff,  Marcuse,  Velisch).  Kausch  observed  the 
extremely  interesting  fact  that  in  birds  hyperglycemia  may  reach 
much  higher  figures — up  to  0.5  per  cent. — than  in  mammals  with- 
out causing  glycosuria.  This  doubtless  is  the  reason  why  the 
urine  after  operations  on  birds  (pigeons  and  ducks)  has  sometimes 
been  found  free  from  glucose.  The  normal  glycemia  in  birds 
seems  to  amount  to  only  0.14  or  0.15  per  cent.  (Kausch). 

For  the  details  of  the  operation  reference  may  be  made  to  the 
special  works.  The  technical  difficulties  are  quite  considerable,  and 
the  object  of  the  experiment  is  often  frustrated  by  necrosis  of  the 
duodenum  and  other  complications.  The  French  experimenters 
have  generally  injected  paraffin,  asphalt,  etc.,  into  the  pancreatic 
duct,  resulting  in  atrophy  and  induration  of  the  gland,  and  a 
couple  of  weeks  afterward  they  have  performed  the  operation  of 
extirpation. 

I  here  follow  chiefly  Minkowski ;  the  facts,  when  no  mention  is 
made  to  the  contrary,  refer  to  the  dog. 

Glycosuria  generally  begins  a  couple  of  hours,  sometimes  much 
later,  after  the  operation  ;  in  50  per  cent,  of  the  cases  it  appears 
within  five  hours  (Lepine).      It  generally  reaches  its   maximum  on 


1 66  DIABETES    MELLITUS    AND    GLYCOSURIA. 

the  third  day,  with  from  lo  to  12  percent.*  of  glucose  in  about  1.5 
hters  of  urine.  The  hyperglycemia  may  reach  0.9  per  cent.,  but 
rarely  exceeds  0.5  per  cent.  As  already  mentioned,  the  relation  be- 
tween the  hyperglycemia  and  the  glycosuria  is  not  a  fixed  one,  and 
some  influence  on  the  part  of  the  kidneys  must  be  admitted.  If  the 
animals  escape  other  complications,  the  glycosuric  dystrophy  leads 
in  a  few  wrecks  to  diabetic  coma. 

If  any  considerable  part  of  the  pancreas — one-eighth  or  one- 
twelfth — is  left,  diabetes  does  not  result.  Hedon  found  the  reten- 
tion of  even  about  one-thirtieth  sufificient  to  prevent  the  develop- 
ment of  the  glycosuria.  By  leaving  a  small  part  of  the  gland  one 
may  restrict  the  effect  to  a  slight  glycosuria  or  to  a  mild  diabetes, 
and  it  has  been  found  that  all  the  different  stages  of  the  glycosuric 
dystrophy  may  be  effected  by  resection  of  the  pancreas. 

Chauveau  and  Kaufmann  have  found  that  if  the  spinal  cord  is 
divided  in  the  lower  cervical  or  upper  thoracic  region  before  extir- 
pation of  the  pancreas,  the  operation  is  not  followed  by  glycosuria. 
I  shall  recur  later  to  their  experiments  and  conclusions. 

Hedon  and  Thiroloix  both  are  of  the  opinion  that  a  gradual  and 
slow  destruction  of  the  pancreas  (by  injections  of  different  sub- 
stances into  it)  may  take  place  without  causing  glycosuria  (?). 

Fever  diminishes  and  phloridzin  increases  the  glycosuria  follow- 
ing extirpation  of  the  pancreas. 

The  sugar  in  the  urine  has  been  proved  to  be  glucose,  not  mal- 
tose. 

When  carbohydrates  are  excluded  from  the  food  after  total 
extirpation  of  the  pancreas,  there  gradually  arises  a  fixed  relation 
between  the  glucose  and  the  nitrogen  in  the  urine,  a  relation  which 
is  represented  by  the  figures  2.8:1.  When  carbohydrates  are 
given,  it  seems  that  during  the  highest  intensity  of  the  dystrophy 
all  the  glucose  produced  is  excreted,  and  this  fact  and  the  fixed 
relation  between  the  glucose  and  the  nitrogen  in  the  urine  during 
exclusion  of  carbohydrates  would — if  one  does  not  accept  the 
presence  in  the  hXoodi  oi  2.  ^' iiiatcria  peccans'' — seem  to  indicate 
that  with  the  destruction  of  the  pancreas  something  is  lost  to  the 
organism  that  is   necessary  for  the   combustion  of  every  molecule 

*  Hedon,  by  giving  only  bread  as  food,  increased  the  glycosuria  to  22  per  cent. 


DIABETES    MELLITUS    AFTER    KEMOVAL    OF    PANCREAS.  l6j 

of  glucose.  During  other  periods  of  the  diabetes  following  total 
extirpation  of  the  pancreas,  however,  according  to  all  researches,  a 
certain  part  of  the  ingested  glucose  is  used  up  in  the  organism. 
Then, — though  the  conditions  for  the  production  of  glucose  from 
proteids  are  not  fully  known, — theoretically,  out  of  lOO  grams  of 
proteid,  minus  the  carbon  necessary  for  the  production  of  urea, 
there  might  be  produced  213  grams  of  glucose  and  only  16  grams 
of  nitrogen — z.  e.,  much  more  than  only  2.8  times  as  much  glucose 
as  nitrogen. 

It  thus  seems  that  though  the  pancreas  is  proved  to  have  a 
specific  function  in  the  utilization  and  combustion  of  glucose,  it 
may  not  be  alone  concerned  in  this  phase  of  bodily  activity. 

Minkowski,  after  giving  large  amounts  of  levulose,  observed 
increased  glycosuria,  but  found  that  a  smaller  part  of  this  mono- 
saccharid  had  passed  unchanged  into  the  urine.  After  200  grams 
of  levulose  by  the  mouth  the  urine  contained  105.6  grams  of 
glucose  and  15.6  grams  of  levulose.  There  were  7.8  grams  of 
nitrogen,  so  that  21.84  grams  (7.8  X  2.8)  of  glucose  were  derived 
from  proteids.  The  rest — 83.76  grams  of  glucose — was  thus 
derived  from  the  levulose. 

Minkowski  failed,  after  giving  considerable  amounts  of  maltose, 
saccharose,  and  lactose,  to  find  any  of  these  disaccharids  in  the 
urine  unchanged,  probably  because  the  quantities  were  not  large 
enough  ;  in  fact,  none  of  them  seems  to  have  been  given  in  as 
large  amount  as  the  levulose.  The  glycosuria  was  increased  by 
all  three  of  the  disaccharids. 

After  extirpation  of  the  pancreas  the  animals  quickly  lose  flesh, 
sometimes  in  the  course  of  a  fortnight  losing  more  than  one-third 
of  their  bodily  weight.  This  is  a  necessary  effect  of  the  deficient 
digestion  and  of  the  enormous  glycosuria.  Abelmann  found  43 
per  cent,  of  fat  ingested  in  emulsion,  almost  all  other  fat  and  56 
per  cent,  of  ingested  proteid  in  the  feces,  which  also  contained 
large  quantities  of  undigested  bread.  Kaufmann  found  that  dia- 
betic dogs  of  from  8  to  15  kilograms  in  weight,  subjected  to  abso- 
lute starvation,  lost  from  250  to  500  grams  in  weight  a  day,  while 
normal  dogs  of  the  same  size  under  similar  circumstances  lost  only 
between  160  and  175  grams. 

Glycosuria  and  impaired  digestion,  according  to  the  opinion  of 


1 68  DIABETES    MELLITUS    AND   GLYCOSURIA. 

most  investigators,  are  not  the  only  causes  of  autophagy  in  these 
and  in  other  cases  of  severe  diabetes.  A  third  cause  is  the  almost 
universally  diCCQ^ied  protoplasmic,  toxic  disintegration  of  the  proteid 
cellular  substances  of  the  organism. 

Minkowski  failed  in  some  cases  after  total  extirpation  of  the  pan- 
creas to  find  diacetic  acid  and  /S-oxybutyric  acid  in  the  urine,  both 
of  which,  so  far  as  my  experience  goes,  are  constantly  found  in 
equally  severe  cases  in  man.  Further  investigations  in  this  respect 
seem  necessary,  but  it  is  possible  that  the  production  of  these  acids, 
which  certainly  are  in  some  way  connected  with  the  excretion  of 
glucose  produced  by  proteids,  is  governed  by  other  conditions  in 
the  dog  than  in  human  beings.  The  diabetic  animals  completely 
oxidize  ingested  acetone  (Schwarz),  but  the  ingestion  of  diacetic 
acid  (Schwarz)  and  of  /5-oxybutyric  acid  (Minkowski)  is  followed 
by  acetonuria. 

The  lactic  acid  in  the  muscles  was  found  to  be  greatly  dimin- 
ished. The  glycogen  was  also  greatly  reduced  in  the  liver  and  in 
the  muscles — probably  on  account  of  the  acidosis,  which  in  most 
cases  was  quite  pronounced.  Syzygium  jambulanum  had  no  de- 
creasing effect  upon  the  glycosuria. 

The  diabetes  following  extirpation  of  the  pancreas  is  a  direct 
effect  of  the  removal  of  the  gland.  It  does  not  result  from  the 
absence  of  the  pancreatic  juice,  for  ligation  of  the  pancreatic  duct  or 
the  production  of  a  fistula  through  which  the  juice  is  conducted 
outside  the  organism  causes  no  diabetes.  Neither  does  the  dys- 
trophy result  from  a  lesion  of  the  solar  plexus,  as  has  been  sup- 
posed. Minkowski  proved  this  theory  to  be  false  by  leaving  a  part 
of  the  pancreas  in  connection  with  its  vessels  outside  the  perito- 
neal cavity  under  the  skin,  without  the  development  of  diabetes, 
while  subsequent  removal  of  this  remaining  piece  of  pancreas  was 
followed  by  the  customary  diabetes. 

Either  the  removal  of  the  pancreas  causes  something  to  disap- 
pear from  the  blood  that  is  necessary  for  the  normal  combustion 
and  utilization  of  the  sugar,  or  it  causes  something  to  remain  in  the 
blood  that  prevents  the  combustion  and  utilization  of  sugar. 

It  has  been  proved  that  injection  of  diabetic  blood  into  the  veins 
of  a  healthy  animal  does  not  produce  even  transitory  diabetes.      On 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 69 

the  other  hand,  it  was  shown  by  Claude  Bernard  that  the  normal 
blood  contains  something  that  causes  the  sugar  in  it  to  disappear 
after  it  has  been  for  some  time  outside  the  organism.  These  facts 
have  led  many  to  the  acceptance  of  a  theory  that  extirpation  of  the 
pancreas  causes  diabetes  by  removing  something  that  is  produced 
in  the  pancreas  as  an  "  internal "  secretion  and  is  given  up  to  the 
blood,  where  its  presence  is  necessary  for  the  combustion  of  the 
sugar.  Lepine  and  his  disciples,  and  even  some  of  his  antagonists, 
found  that  the  blood  of  dogs,  diabetic  after  extirpation  of  the  pan- 
creas, both  within  and  without  the  organism,  loses  its  sugar  less 
quickly  than  does  normal  blood.  Kausch  saw  an  analogous 
phenomenon  in  birds.  Schwarz  found  that,  though  dogs  after  extir- 
pation of  the  pancreas  seem  to  oxidize  as  large  amounts  of  acetone 
as  normal  dogs,  the  former,  diabetic  dogs,  unlike  normal  dogs, 
after  ingestion  of  diacetic  acid  exhibited  acetonuria.  All  this  has 
strengthened  the  position  of  those  who  consider  diabetes  an  effect 
of  decreased  consumption  of  sugar.  In  the  next  chapter  we  shall 
find  that,  even  if  these  observations  are  correct,  they  alone  do  not 
settle  the  question  of  the  immediate  causes  of  diabetes — a  question 
the  solution  of  which  is  one  of  the  most  difficult  and  complicated 
tasks  that  are  at  present  engaging  the  attention  of  students  of  experi- 
mental pathology. 


CHAPTER  VII.— METABOLISM  AND  NUTRITIVE  NEEDS. 

Notwithstanding  the  progressive  strides  that  have  been  made 
in  recent  years,  the  metabolic  changes  that  take  place  in  diabetes 
are  but  imperfectly  known. 

By  following  as  well  as  we  can  the  carbohydrates,  the  fat,  and 
the  proteids  on  their  way  through  the  organism  we  may,  however, 
obtain  a  conception  of  the  respective  processes,  which  is  not  with- 
out considerable  theoretic  and  practical  value.  In  doing  this  we 
must  not  omit  to  give  some  attention  to  corresponding  processes  in 
normal   orcranisms  :  neither  must  we   lose  sieht  of  the  differences 


I/O  DIABETES    MELLITUS    AND   GLYCOSURIA. 

between  cases  of  mild  and  severe  diabetes — /.  e.,  between  the  patient 
that  excretes  sugar  only  after  ingestion  of  carbohydrates  and  the 
one  that  exhibits  glycosuria  at  the  expense  of  proteids,  and  with  a 
diet  consisting  exclusively  of  these  and  of  fat. 

We  have  already  seen  that  in  the  great  majority  of  diabetic 
cases  digestion  is  perfectly  normal.  In  such  cases  Pautz  recently 
found  7.59  per  cent,  loss  of  nitrogen  and  3.54  per  cent,  loss  of  fat. 
The  maximum  and  minimum  figures  for  nitrogen  were  12.97  and 
1.74 ;  for  fat  they  were  9.12  and  1.06 — i.  e.,  just  about  what  we  are 
accustomed  to  see  designated  as  normal.  As  to  carbohydrates, 
Heller,  as  early  as  1852,  showed  that  they  are,  as  a  rule,  normally 
digested  in  cases  of  diabetes,  and  Hirschfeld's  cases  prove  that  this 
often  takes  place,  even  when  digestion  of  proteids  and  fat  is  im- 
paired. Of  ingested  starch,  normally  from  i  to  7.4  per  cent, 
appears  undigested  in  the  feces. 

The  normal  changes  that  carbohydrates  undergo  in  the  alimentary  canal 
must  be  borne  in  mind.  Starch  (or  glycogen)  digested  by  the  mixed  saliva  (or 
by  the  secretion  of  the  parotid  gland  alone)  yields  achroodextrin  and  maltose* 
and  only  small  quantities  of  glucose  (Musculus  and  v.  Mering,  Kiilz).  The 
diastatic  ferment  found  in  the  stomach  in  the  acid  gastric  juice  is  not  very 
active ;  but  in  the  duodenum  the  pancreatic  juice  is  most  efficient  in  the  same 
way  as  the  saliva.  The  final  products,  however,  of  the  digested  starch,  found 
almost  entirely  in  the  portal  system  and  only  in  comparatively  minute  quanti- 
ties in  the  lymphatics,  consist  almost  exclusively  of  glucose,  together  with  some 
traces  of  dextrin  and  maltose  (C.  Voit,  Bleile,  v.  Mering),  whether  this  result 
has  been  brought  about  by  the  "  invertin  "  from  the  mucous  membrane  of  the 
bowels  (Tebb),  or  by  the  epithelium  itself  (Bunge),  or  by  the  blood  (Bial,  Roh- 
mann). 

Cane-sugar  partly  is  decomposed  into  glucose  and  levulose,  partly  remains 
unchanged  in  the  stomach,  and  is  so  far  absorbed  in  this  state ;  in  the  duodenum 
this  part  of  the  disaccharid  is  also  quickly  decomposed  into  its  monosaccharid, 
levulose,  and  glucose  by  the  pancreatic  juice  (Kobner).  When  taken  in  large 
amounts  like  all  saccharids  it  remains  unchanged  for  some  small  part  as  cane- 
sugar,  not  only  in  the  bowels,  but  in  its  passage  through  the  whole  organism, 
and  it  is  found  as  such  in  the  urine. 

Maltose  probably  is  already  changed  in  the  bowels  into  glucose  (Voit). 

Lactose,  so  far  as  it  is  not  changed  into  lactic  acid,  etc.,  probably  remains 
in  large  part  unchanged  in  the  alimentary  canal  (Lusk) ;  the  different  results 
of  numerous  researches  seem  to  me  to  indicate  great  individual  and  accidental 

''' Disaccharids  and  Monosaccharids.  Maltose  :=  glucose  -}-  glucose.  Cane-sugar  = 
glucose   -j-  levulose.     Lactose  ^  glucose  +  galactose  (Hammarsten). 


METABOLISM    AND    NUTRITIVE    NEEDS. 


171 


variations.  Lactose  passes  unchanged  into  the  urine  after  smaller  amounts 
are  taken  than  do  the  other  saccharids  (G.  Voit,  Bischoff,  Hofmeister,  and 
others),  and  does  often  so  during  lactation. 

In  chickens  and  rabbits  levulose  seems  to  be  absorbed  in  an  unchanged 
state  (Fr.  Voit,  Lusk,  Otto).  Like  all  other  saccharids,  it  passes  partly  un- 
changed into  the  urine  after  large  amounts  have  been  taken. 

Cane-sugar  and  maltose  are  in  larger  part  (70  or  80  per  cent.)  absorbed 
during  the  first  hour  after  ingestion.  Glucose  seems  to  remain  a  little  longer, 
but  lactose  a  less  time  in  the  stomach. 

These  results  are  gained  chiefly  in  dogs  whose  food  and  digestion  are  simi- 
lar to  man's.  Still,  there  seem  to  be  differences,  and  normal  dogs  seem  to 
excrete  glucose  after  the  ingestion  of  large  amounts  of  cane-sugar,  which  is  not 
the  case  with  man.  Rubner,  by  feeding  dogs  with  cane-sugar  exclusively, 
found  almost  only  this  disaccharid  in  the  urine  on  the  first  day,  but  afterward 
gradually  more  and  more  glucose.  Seegen  found  in  dogs  after  the  ingestion  of 
cane-sugar  this  saccharid  in  part  in  its  unchanged  state,  in  part  as  invert- 
sugar  (=  glucose  -f-  levulose),  while  Praussnitz  made  the  same  observation  in 
chickens. 

Lusk  obtained  the  following  results  six  and  one-half  hours  after  the  inges- 
tion of  30  grams  of  cane-sugar  by  rabbits  : 


Cane-sugar. 

Glucose. 

Levulose. 

Stomach, 

0.269 

1.498 

0.858 

Duodenum  and  jejunum,             .    . 

0.002 

Traces. 

Traces. 

Cecum, 

0. 

0.846 

1. 321 

Colon  and  rectum, 

0. 

Small  amounts. 

Small  amounts. 

With  regard  to  the  digestion  of  fat  it  must  be  remembered  that  during  an 
abundant  supply  of  easily  digestible  quality,  often  only  1.5  per  cent.,  rarely 
more  than  from  4  to  6  per  cent.,  is  lost ;  that  fat  with  a  low-melting  tempera- 
ture is  absorbed  better  and  more  quickly  than  fat  with  a  high-melting  tempera- 
ture (Miiller  and  Arnschink)  ;  that  the  presence  of  free  fatty  acids  facilitates 
absorption,  in  which  process  both  bile  and  the  pancreatic  juice  are  of  great 
importance,  if  the  fat  is  not  ingested  in  a  state  of  emulsion  (Levin,  Buchheim) ; 
that  a  mixed  diet  promotes  absorption,  though  the  most  advantageous  relation 
in  the  quantities  of  the  different  kinds  of  food  has  not  yet  been  determined 
(Rosenheim,  Munk).  Finally,  it  is  known  that  catarrhal  conditions  first  impair 
the  absorption  of  fat,  while  proteids  and  carbohydrates  still  continue  to  be 
absorbed  normally  (Fr.  Miiller).  Individual  and  accidental  circumstances  have 
a  great  influence  even  under  normal  conditions. 

We  shall  here  entirely  pass  over  the  highly  complicated  chemic  processes 
by  which  the  ingested  proteids  are  converted  ultimately  into  albumoses  and 
peptones,  as  well  as  the  manner  in  which  these  substances  are  absorbed  in  con- 
sequence of  the  specific  cellular  activity  of  the  mucous  membrane.     There  are 


1/2  DIABETES    MELLITUS    AND    GLYCOSURIA. 

in  this  respect  no  known  or  even  suspected  differences  between  the  diabetic 
and  the  normal  individual,  nor  in  the  processes  by  which  the  albumoses  and 
the  peptones  are  again  changed  into  true  albumin  in  its  different  modifications. 
According  to  differences  in  the  quality  of  the  food,  from  3  to  5,  or  from  6  to  10 
per  cent.,  or  even  more,  of  the  proteids  may  normally  remain  undigested  in 
the  intestines  (Rubner).  During  the  passage  of  proteids  through  the  aliment- 
ary canal  there  are  formed,  as  is  known,  many  substances  that  are  not  proteids 
(leucin,  tyrosin,  tryptophan,  amido-acids,  asparagic  acid)  ;  in  the  colon  and 
rectum  are  found  a  whole  series  of  "  aromatic  "  substances  and  other  products 
of  putrefaction  (indol,  skatol,  parakresol,  phenol,  phenyl-propionic  acid, 
phenyl-acetic  acid,  paraoxyphenyl-acetic  acid,  hydroparacumaric  acid,  free 
fatty  acids,  carbonic  acid,  marsh-gas,  hydrogen  sulphid,  etc.).  Often  secret- 
ing a  smaller  amount  of  bile  than  normal,  and  partaking  of  food  rich  in  pro- 
teids and  often  suffering  from  habitual  constipation,  which  allows  of  a  longer 
period  for  putrefactive  process,  diabetics  are  likely  to  produce  large  quantities 
of  the  aromatic  substances  mentioned.  In  consequence  their  urine  usually 
contains  large  quantities  of  "  ethereal  "  combined  sulphates  resulting  from 
the  oxidation  of  the  "aromatic"  substances.* 

When  with  an  ordinary  diet  the  ingested  carbohydrate,  changed 
into  glucose  (together  with  some  small  quantities  of  dextrin, 
maltose,  and  perhaps  still  other  carbohydrates),  is  carried  by  the 
blood  in  the  portal  vein  to  the  liver,  it  there  forms  the  anhydrid  of 
glucose  or  glycogen, f  and  to  this  most  important  substance  we 
must  devote  a  good  deal  of  attention. 

It  seems  certain  that  not  all  the  glucose  carried  by  the  portal  vein 
to  the  liver  is,  under  all  circumstances  or  at  once,  transformed  into 

*  The  phenols,  skatol,  and  indol  are  oxidized  in  the  organism  and  pass  into  the  urine 
as  indoxyl-sulphuric  and  skatoxyl-sulphurlc  acids.  The  quantity  of  these  and  other 
ethereal  sulphates  normally  equals  about  0.25  gram  a  day,  and  bears  a  ratio  to  the  sul- 
phuric acid  of  the  sulphates  of  I  :  lo  (from  I  :  15  up  to  I  :  67). 

f  Glycogen,  as  is  well  known,  is  a  polysaccharid  closely  related  to  starch  ;  its  formula 
probably  is  6(CgH,Q05)  +  H^O  (Kiilz).  Under  the  influence  of  dilute  acids  it  is  entirely 
changed  into  the  monosaccharid  glucose ;  saliva  and  pancreatic  juice  transform  it  into 
achroodextrin,  maltose,  and  small  quantities  of  glucose.  In  the  cells  of  the  liver  gly- 
cogen is  uniformly  diffused  in  small  granules  embedded  in  larger  granules  of  the  so-called 
paraplasm  (Kupfer),  an  imperfectly  known  substance,  probably  representing  a  form 
intermediate  between  glycogen  and  its  mother-substances.  The  muscles  constitute  the 
other  important  repository  of  glycogen,  containing  about  as  much  as  the  liver;  it  is 
present  in  the  interfibrillary  substance  (Frerichs).  From  whatever  substance  glycogen  is 
formed  it  is  itself  completely  homogeneous  (Salomon,  Luchsinger,  Otto).  Still,  there 
is  some  difference  between  the  glycogen  of  the  liver,  which  is  colored  brownish-red  by 
tincture  of  iodin,  and  the  glycogen  of  the  muscles,  which  with  the  same  tincture 
develops  rather  a  violet  color. 


METABOLISM    AND    NUTRITIVE    NEEDS.  1/3 

glycogen.  After  the  ingestion  of  large  amounts  of  glucose  even 
normal  individuals  excrete  some  glucose  in  the  urine.  Under  ordi- 
nary and  normal  circumstances  a  considerable  part  of  the  glucose 
may  also  pass  through  the  liver  and  be  either  used  immediately  in 
the  tissues  or  stored  as  glycogen  in  the  muscles  or  elsewhere,  or  it 
may  return  to  the  liver  and  be  stored  there  after  having  passed 
through  the  whole  circulation.  It  is  certain  that  the  glycogen  in 
the  liver  continues  increasing  for  a  much  longer  time  after  the  in- 
gestion of  carbohydrate  than  the  glucose  needs  to  pass  through  the 
whole  organism.  After  the  ingestion  of  a  large  amount  of  glucose 
the  glycosuria  appears  within  thirty  or  forty  minutes  ;  after  the  in- 
gestion of  syrup  the  maximum  amount  of  glycogen  in  the  liver  is 
reached  (in  rabbits)  only  after  from  sixteen  to  twenty  hours  (Kiilz). 
After  the  ingestion  of  small  amounts  six  hours,  and  after  the  in- 
gestion of  large  amounts  from  twelve  to  sixteen  hours,  elapse  before 
this  maximum  is  reached  in  chickens  (Hergenhahn).  The  liver 
generally  stores  its  maximum  long  before  the  muscles  acquire 
theirs  ;  after  the  ingestion  of  very  large  amounts,  however,  the 
glycogen  is  stored  about  as  quickly  by  the  latter  as  by  the  liver 
(Hergenhahn). 

Glycogen  is  formed  in  the  liver  from  both  carbohydrates  and 
proteids,  and  its  amount  can  be  maintained  or  increased  there  by 
many  different  substances.  Glucose  and  levulose  (or  starch)  yield 
the  highest  values,  up  to  20  per  cent,  or  even  more.  Those  sac- 
charids  that  do  not  ferment  with  yeast  do  not  yield  more  than  a 
small  percentage. 

The  researches  on  the  formation  of  glycogen,  since  its  discovery  in  1857, 
already  represent  an  enormous  amount  of  work,  and  the  subject  certainly  will 
be  the  object  of  further  investigation.  The  experiments  consist  in  subjecting 
the  animals  to  starvation  until  the  glycogen  is  supposed  to  be  wholly  con- 
sumed, in  feeding  them  afterward  with  the  substance  in  question,  and,  finally, 
in  determining  the  quantity  of  glycogen  in  the  liver. 

Bernard  proved  that  both  carbohydrates  and  proteids — i.  <?,,  meat  and 
fibrin — produce  glycogen,  Woroschilofif  that  the  latter  is  formed  from  glue. 
[That  carbohydrates  are  formed  from  proteids  can  be  demonstrated  to  any  one 
who  does  not  accept  their  formation  from  fat  by  the  fact  that  diabetics  in  the 
severe  stage  continue  for  months  to  excrete  more  glucose  than  can  possibly  be 
made  up  by  the  carbohydrates  in  their  food.]  Kiilz's  "  Beitrage  zur  Kenntniss 
des  Glycogens,"  Marburg,  1891,  contains  a  good  exposition  of  what  has  been 
done  in  this  connection  by  Bernard,  Stokvis,  MacDonnell,  Tcherinoff,  Hoppe, 


1/4  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Doch,  Weiss,  Luchsinger,  Naunyn,  Nencki,  Wolfberg,  v.  Mering,  Finn, 
Pfliiger,  Hergenhahn,  Nebelthau,  and  by  Kiilz  himself,  who  fed  chickens  with 
muscle,  fibrin,  casein,  serum-albumin,  and  egg-albumin.  The  last-named  thus, 
beyond  a  doubt,  proved  that  these  substances  yielded  from  i  to  2.5  per  cent,  of 
glycogen  in  the  liver.  Pavy  (in  rabbits)  with  starch  and  cane-sugar  succeeded 
in  depositing  27.6  per  cent,  of  glycogen  in  the  liver;  with  starch,  cane-sugar, 
and  albumin  the  amount  was  17  per  cent.  Meat  yielded  at  the  utmost  7  per 
cent.,  gum-arabic  q  per  cent.,  gelatin  traces,  and  olive  oil  also  only  traces 
(probably  remaining  from  before  the  experiment).  MacDonnell's,  Tcheri- 
noffs,  and  Seegen's  experiments  led  to  similar  results.  Seegen  besides  found 
1.67  per  cent,  of  glycogen  in  the  liver  of  dogs  after  eight  days  without  food, 
and  after  feeding  the  animals  during  the  following  eight  days  exclusively  on 
fat  in  large  quantities  he  found  0.93  per  cent.  Kiilz,  in  chickens  fed  with  cane- 
sugar,  found  8.24  per  cent. ;  with  glucose  6.63  per  cent. ;  with  levulose  6.07  per 
cent. ;  with  galactose  3.28  per  cent.,  and  with  lactose  2.32  per  cent,  of  glycogen 
in  the  liver.  Kausch  and  Socin  (1898)  have  found  as  much  as  9  per  cent,  with 
lactose. 

It  will  thus  be  seen  that  the  power  of  the  different  saccharids  to 
form  glycogen  in  the  liver  in  normal  individuals  does  not  bear  any 
relation  to  their  power  of  causing  glycosuria  in  diabetics.  Glucose 
and  levulose  normally  yield  about  the  same  amount  of  glycogen,  but 
glucose  causes  much  greater  glycosuria  in  diabetes  than  does  levu- 
lose. The  glycogen  in  the  liver  in  diabetics  again  is  increased  in  much 
greater  degree  by  levulose  than  by  glucose  (Sandmeyer) — a  quality 
of  the  levulose,  which  presumably  is  the  cause  for  its  producing  less 
glycosuria  in  such  individuals.  The  more  easily  a  saccharid  under- 
goes fermentation  the  more  glycogen  it  forms  normally,  according 
to  C.  Voit ;  the  less  it  normally  passes  into  the  urine,  according  to 
Cremer  ;  and  the  better  it  forms  fat,  according  to  Liebig. 

It  is  in  many  respects  interesting  to  learn  the  effect  of  subcuta- 
neous injections  of  different  saccharids.  Fritz  Voit,  in  1896,  made 
such  injections  (of  ten  per  cent,  solutions)  of  monosaccharids  :  levu- 
lose, galactose,  and  glucose  ;  and  of  the  disaccharids  :  maltose,  lac- 
tose, and  cane-sugar.  All  of  the  monosaccharids  were  completely 
consumed  in  the  tissues  even  after  the  injections  of  considerable 
amounts.  After  the  injection  of  large  amounts  a  small  quantity 
appeared  unchanged  in  the  urine.  Thus,  the  injection  of  60  grams 
of  glucose  yielded  a  trace  of  glucose  in  the  urine,  while  the  injec- 
tion of  100  grams  yielded  2.6  grams  of  glucose  in  the  urine. 
Maltose,  too,  was  readily  consumed.  The  disaccharids,  cane-sugar 
and  lactose,  however,  were  not  consumed,  and  passed  almost  com- 


METABOLISM    AND    NUTRITIVE    NEEDS.  1/5 

pletely  through  the  organism,  and  appeared  unchanged  in  the 
urine.  Only  the  monosaccharids  and  the  disaccharid,  maltose, 
whose  molecules  are  believed  to  consist  of  two  molecules  of 
glucose,  seem  to  form  glycogen  without  being  first  changed.  Cane- 
sugar  can  be  stored  as  glycogen  in  the  liver  only  after  being  con- 
verted into  glucose  and  levulose,  lactose  only  after  being  converted 
into  glucose  and  galactose. 

Besides  the  substances  already  mentioned,  Kiilz  found  that  the  following 
substances  also  have  some  power  of  maintaining  glycogen  in  the  liver :  Raf- 
finose,  glycerin,  gum-arabic,  sorbin,  ethylene,  glycol,  erythrite,  dulcite,  man- 
nite,  inosite,  saccharin,  isosaccharin,  dextronic  acid,  saccharic  acid,  mucic 
acid,  glycuronic  acid,  calcium  dextronate,  sodium  tartrate,  and  citrate.  Urea 
also  yielded  glycogen.  Inulin  yielded  small  quantities  and  olive-oil  traces. 
Nebelthau  found  some  power  of  maintaining  glycogen  in  the  liver  in  ammo- 
nium citrate  carbonate,  lactate,  and  formate  in  benzamid  and  formamid,  in 
glycocoUa  and  asparagin,  in  antipyrin,  cairin,  quinin,  and  chloral,  chloramid, 
paraldehyd,  and  sulphonal.  Ether,  chloroform,  and  alcohol  seemed  somewhat 
efficient,  while  urethan  yielded  a  dubious  result.  Cremer  found  that  some 
glycogen  formed  after  use  of  the  pentoses  *  (xylose,  arabinose,  and  rhamnose)  ; 
Salkowski  also  found  some  after  use  of  arabinose;  Fraentzel  obtained  a  com- 
pletely negative  result  from  xylose. 

From  the  foregoing  it  will  be  understood  that  glycogen  can  be 
formed  or  maintained  in  the  liver  in  many  different  ways.  From 
glucose  it  is  formed  by  dehydration,  a  comparatively  large  amount 
resulting.  Lactose  forms  glycogen  only  indirectly,  after  having 
been  divided  into  its  monosaccharids  ;  but  though  a  large  part  of 
the  ingested  lactose  may  have  been  changed  into  lactic  acid  before 
this  happens,  the  rest  usually  gives  rise  to  the  presence  of  quite 
considerable  quantities  of  glycogen  in  the  liver  (Kausch  and  Socin). 
Olive-oil  and  other  fatty  substances,  which  are  believed  to  main- 
tain the  glycogen  in  the  liver  only  by  undergoing  oxidation  them- 
selves, seem  to  afford  very  little  protection  for  it.  As  for  the  power 
of  antipyrin  to  maintain  glycogen  in  the  liver,  this  must  be  derived 

*  The  pentoses  do  not  seem  to  promise  the  diabetic  patient  anything.  Ebstein  found 
arabinose  and  xylose  unchanged  in  the  urine  after  quite  small  doses.  Lindemann  and 
May  found  about  eight  per  cent,  of  rhamnose  unchanged  in  the  urine  of  normal  indi- 
viduals. Sixty-five  grams  of  rhamnose  caused  some  glycosuria  in  a  diabetic  patient 
previously  free  from  it ;  besides  7.27  grams  of  rhamnose  appeared  in  the  urine  and  2.85 
grams  in  the  feces.  Rhamnose  is  suspected  of  having  no  wholesome  influence  on  the 
kidneys. 


1/6  DIABETES    MELLITUS    AND    GLYCOSURIA. 

from  some  specific  influence,  and  can  result  neither  from  direct  for- 
mation nor  from  oxidation. 

The  glycogen  in  the  muscles  is  formed  in  and  by  the  muscles 
themselves  from  the  sugar  of  the  blood.  It  may,  perhaps,  be  fur- 
nished to  them  also  to  some  small  extent  as  glycogen.  Bohm  and 
Hoffmann  found  0.4  per  cent,  in  the  cat ;  Hasse  between  0.4  and 
0.9  per  cent,  in  dogs,  cats,  and  rabbits.  Kiilz  considered  these 
figures  somewhat  too  small. 

The  glycogen  in  the  liver  and  the  glycogen  in  the  muscles  are, 
under  ordinary  circumstances,  about  equal  in  amount,  and  together 
make  up  the  organism's  whole  store  of  this  substance,  except  a 
comparatively  insignificant  amount  in  other  tissues.  The  storage 
in  the  liver  and  the  storage  in  the  muscles  depend  on  the  same 
influences,  and  are  both  increased  or  decreased  by  the  same  causes. 
The  glycogen  of  the  muscles  manifests  greater  stability,  and  is 
slower  both  in  increasing  and  in  decreasing.  Heat  increases  the 
glycogen,  and  rest  has  the  same  influence.  By  severing  the  cen- 
tral from  the  peripheral  nervous  system  glycogen  is  stored  in  great 
quantity,  partly  on  account  of  the  paralysis  of  the  muscles,  partly, 
perhaps,  on  account  of  the  withdrawal  of  other  nervous  influences 
(Claude  Bernard,  Nebelthau).  Cold  diminishes  the  amount  of  glyco- 
gen and  is  capable  of  causing  its  disappearance  from  both  liver  and 
muscles  in  thirty  hours  (Bohm  and  Hoffmann).  Mechanical  work 
is  most  effective  in  the  same  direction.  Weiss  found  only  about 
half  as  much  glycogen  in  tetanized  muscle  as  in  the  corresponding 
muscle  at  rest.  Chauveau  and  Kaufmann  had  a  similar  experience. 
Rosenbaum,  Demant,  and  Hergenhahn  saw  the  glycogen  almost 
totally  disappear  during  the  convulsions  from  poisoning  with 
strychnin  ;  and  Kiilz  found  the  glycogen  in  both  its  great  store- 
houses reduced  to  a  minimum  after  a  short  period  of  starvation 
and  hard  work  combined.  Starvation  decreases  the  glycogen. 
Kiilz,  however,  still  found  traces  of  it  in  the  liver  and  somewhat 
more  in  the  muscles  of  the  dog  after  twenty  days  of  abstinence 
from  food.  After  extirpation  of  the  liver  the  glycogen  suddenly 
decreases  in  the  muscles  (Laves).  Acids  in  the  blood  decrease 
and  alkaline  salts  increase  the  amount  of  glycogen  (Kiilz).  After 
ligature  of  the  choledoch  duct  with  biliary  stasis  the  glycogen  dis- 
appears from  the  liver  and  is  not  formed  again  (Frerichs,  Wick- 


METABOLISM    AND    NUTRITIVE    NEEDS.  1/7 

ham  Legg).  After  death  glycogen  disappears  from  the  Hver  and 
(somewhat  more  slowly)  from  the  muscles.  Praussnitz,  after  only 
half  an  hour,  found  75  per  cent,  of  the  original  amount.  Werther, 
after  three  hours,  found  scarcely  anything  left.  This  change  takes 
place  more  quickly  in  a  warm  than  in  a  cold  room. 

In  the  blood  the  glycogen  is  found  in  the  leukocytes  ;  a  liter  con- 
tains only  about  0.0 1  gram  (Huppert).  The  lymphatics  also  con- 
tain a  small  quantity  (Frerichs).  Glycogen  has  besides  been  found 
in  the  skin  (Paschutin),  in  the  hair-bulbs  (Neisser),  in  the  kidneys 
(Wiersma,  Paschutin,  Abeles,  Ehrlich),  in  the  spleen  (Hoppe- 
Seyler),  in  the  lungs  (Abeles),  in  the  testicles  (Kiihne),  and  in  new 
growths  (Hoppe-Seyler,  Brault).  It  seems  to  occur  especially  in 
inflamed  tissues  (Sotniskewski,  Pavy,  Kiihne),  and  during  this  state 
it  has  also  been  found  in  the  brain  (Paschutin),  where  it  does  not 
seem  to  be  found  normally  (Abeles,  Seegen,  Kratschmer,  Paschutin). 
Finally,  it  is  much  more  abundant  in  embryonic  than  in  fully  devel- 
oped tissues  (Bernard).  In  view  of  this  fact,  and  of  the  further 
fact  that  it  is  found  especially  in  inflamed  tissues  and  in  tumors  of 
rapid  growth,  it  would  seem  to  be  indicative  of  a  condition  of 
energetic  cellular  life. 

It  may  now  be  considered  as  settled  that  in  cases  of  diabetes  the 
amount  of  glycogen  is  diminished  both  in  the  liver  and  in  the 
muscles.  Frerichs,  with  admirable  presence  of  mind,  plunged  a 
trocar  into  the  liver  of  three  submissive  individuals,  of  whom  one 
was  in  good  health  and  the  other  two  were  diabetic.  Although 
the  stage  of  diabetes  is  not  stated,  it  was  probably  an  advanced  one. 
It  was  found  that  between  four  and  one-half  and  five  and  one-half 
hours  after  an  abundant  mixed  meal  the  liver-cells  of  the  healthy 
person  contained  a  large  amount  of  glycogen,  while  those  of  the 
two  diabetics  contained  a  moderate  amount  and  a  very  small 
amount,  respectively.  Both  the  liver  and  the  muscles  of  diabetic 
dogs  contain  little  glycogen  (v.  Mering,  Minkowski,  Sandmeyer). 
Pieces  of  liver  excised  shortly  after  death  in  diabetic  coma  were 
found  to  contain  very  little  glycogen  (Frerichs)  ;  and  it  could  not 
be  found  at  all  in  the  muscles  of  such  patients  (Abeles).  The 
diabetic  liver  in  a  state  of  fatty  degeneration  seems  to  contain  the 
smallest  amount  of  glycogen  (Boccardi). 

I  presume  that  if  a  diabetic   in  the   mild   stage  and  a  healthy 


178  DIABETES    MELLITUS    AND    GLYCOSURIA. 

person  receive  the  same  food  with  so  much  carbohydrates  that  the 
diabetic  excretes  sugar  in  his  urine,  the  latter  will  store  less  glyco- 
gen than  the  healthy  person,  and  the  glycogen  will  thus  never  reach 
such  high  figures  as  are  reached  normally  after  the  ingestion  of 
large  amounts  of  carbohydrates.  If,  however,  both  the  diabetic  and 
the  healthy  individual  receive  the  same  food  with  such  restriction 
of  carbohydrates  as  to  render  the  diabetic  free  from  glycosuria,  both 
will  probably  store  the  same  amount  of  glycogen.  The  diabetic 
patient  in  the  severe  stage  always  passes  in  the  urine  glucose  derived 
from  both  the  carbohydrates  and  the  proteids  of  the  food,  and  from 
this  cause  alone  he  possesses  but  a  limited  power  of  storing  glyco- 
gen. In  the  severe  stage,  however,  this  power  is  besides  weakened 
by  the  acidosis,  or  the  presence  in  the  blood  of  diacetic  acid  and 
y9-oxybutyric  acid. 

At  the  same  time  that  the  amount  of  glycogen  is  diminished  in 
the  liver  and  in  the  muscles  in  cases  of  diabetes,  it  is  increased  in 
other  parts  and  elements  of  the  organism,  Gabritschewski  found 
much  more  marked  reaction  for  glycogen  in  the  leukocytes  of  dia- 
betic blood  than  in  those  of  normal  blood  ;  Minkowski  observed 
the  same  fact  in  pus  (0.83  per  cent,  in  diabetics  as  against  0.23  per 
cent,  in  nondiabetics).  The  leukocytes  partly  have  their  own  inde- 
pendent economy  and  store  much  glycogen  from  a  hyperglycemic 
medium.  The  brain,  in  which  glycogen  is  not  normally  found,  con- 
tains this  substance  in  cases  of  diabetes  (see  above).  Ehrlich  first 
demonstrated  the  deposition  of  glycogen  in  the  epithelial  elements 
of  the  kidneys.      Leube  found  it  twice  in  diabetic  urine.* 

The  enormously  important  questions  with  regard  to  the  meta- 
bolism of  glycogen,  and  with  regard  to  the  origin  and  significance 
of  the  glucose  in  the  liver,  have  given  rise  to  a  variety  of  opinions 
and  have  been  the  subject  of  much  controversy.  The  technical 
difficulties  in  solving  these  problems  experimentally  are  very  great, 
and  the  human  obstinacy  in  defending  per  fas  and  nefas  a  position 
once  taken  is  still  greater.  Even  to-day  three  different  main  cur- 
rents of  opinion  may  be  recognized  as  represented  by  the  names 
of  Claude  Bernard,  Pavy,  and  Seegen.     At  present  we  are  justified 


*  Glycogen  is  besides  found  (in  cases  of  diabetes)  in  the  lungs,  in  the  testicles  (Grohe), 
pancreas,  spleen  (Abeles),  in  the  heart,  and  in  the  cartilages  (v.  Mering,  Ewald). 


METABOLISM    AND    NUTRITIVE    NEEDS.  1/9 

in  saying  that  the  theory  advocated  by  Bernard  has  proved  to  be 
much  the  strongest,  and  that  the  vast  amount  of  work  performed 
since  the  fundamental  discoveries  of  this  great  French  physiologist 
and  experimenter  has  tended  to  strengthen  the  opinion  that  if  he 
has  not  demonstrated  the  whole  truth  he  has  certainly  demonstrated 
the  essential  points  of  it.  Pavy's  theory,  denying  entirely  the  phys- 
iologic formation  of  glucose  in  the  liver  and  its  presence  for  pur- 
poses of  vital  power  in  the  blood,  almost  everywhere  belongs  to 
the  past.  Seegen,  who  denies  that  the  glucose  of  the  liver  and  of 
the  blood  (whose  vital  importance  for  the  organism  he  acknowl- 
edges) is  formed  from  glycogen,  and  who  considers  it  to  be  formed 
from  proteids  and  from  fat,  has  gained  comparatively  few  adherents 
to  this  last  view,  in  which  he  deviates  from  Claude  Bernard. 

Claude  Bernard,  in  1877,  summed  up  his  views  on  these  subjects, 
his  theory,  confirmed  and  enlarged  by  later  investigations,  being  as 
follows  :  The  liver  forms  glycogen  from  (a  part  of)  the  carbohy- 
drates and  the  proteids  of  the  food,  and  afterward,  from  this  glyco- 
gen, under  the  influence  of  a  ferment  and  under  the  vasomotor  regula- 
tion of  the  nervous  system,  forms  glucose,  which,  according  to  the 
needs  of  the  organism,  it  delivers  to  the  blood,  of  which  glucose  is 
a  most  important  ingredient.  For  the  production  of  vital  force  the 
glucose  is  then  oxidized  in  the  tissues  into  carbonic  acid  and  water. 
Recent  investigations,  leaving  many  questions  as  to  the  fate  of  glu- 
cose for  solution  in  the  future,  seem  to  confirm  Bernard's  opinion 
that  the  glucose  is  led  to  complete  combustion  through  the  molec- 
ular structure  of  lactic  acid  (Kausch,  Lang),  and  make  it  probable 
that  another  intermediate  station  between  the  glucose  and  its  ulti- 
mate products,  carbonic  acid  and  water,  is  represented  by  the  mole- 
cule of  glycuronic  acid  (Weintraud).  It  has  been  proved  and  is 
universally  accepted  that  fat  is  produced  from  the  superfluous  car- 
bohydrates, and  the  seat  of  this  process  is  believed  to  be  the  liver. 

Of  late,  some  persons,  who  may  be  considered  authorities,  have 
so  far  adopted  Seegen's  theory  as  to  believe  that,  with  a  deficiency 
of  proteids  and  carbohydrates,  fat  may  give  rise  to  the  formation  of 
glucose.  It  seems  to  me  that  the  facts  that  plead  for  such  a  theor}^ 
are  much  weaker  than  those  that  plead  against  it  (see  below). 

The  diastatic  ferment  in  the  liver,  like  all  ferments  not  consist- 
ing of  organisms,  presents  many  mysterious  points  ;    Dastre   goes 


100  DIABETES    MELLITUS    AND    GLYCOSURIA. 

SO  far  as  to  call  it  hypothetic.  All  attempts  to  isolate  it — chiefly 
by  precipitating  it  with  alcohol  after  having  extracted  it  from  the 
liver  with  glycerin — have  failed.  Tiegl  believes  that  it  arises  from 
the  products  of  the  disintegration  of  the  red  blood-corpuscles,  while 
many  believe  it  to  be  fixed  to  the  living  liver-cells.* 

In  a  decoction  of  the  liver  and  in  the  precipitate  thrown  down  by 
absolute  alcohol  from  such  a  decoction  again  dissolved  in  water, 
glucose  is  formed  at  ordinary  temperature,  which  is  not  the  case 
with  a  solution  of  pure  glycogen  (Schwiening).  Bernard  believed 
the  variations  in  the  production  of  glucose  to  depend  on  variations 
in  the  circulation,  and  these  on  nervous,  vasomotor  influences. 
Bial,  who  considers  the  diastatic  ferment  of  the  liver  identical  with 
the  diastatic  ferment  of  the  muscles,  believes  both  to  belong  to  and 
depend  on  the  lymph.  The  diastatic  ferment  in  the  liver  and  in 
the  blood  changes  starch  and  dextrin  and  glycogen,  not  into  mal- 
tose, but  into  glucose,  and  also  converts  maltose  into  glucose. 
In  the  embryo  and  in  the  new-born  child  these  effects,  which 
vary  in  different  species  of  animals,  are  quite  weak.  Sodium  car- 
bonate and  bicarbonate  retard  the  effect  of  the  diastatic  ferment 
on  glycogen  (Gans). 

The  sugar  in  the  liver  has  been  produced  in  substance  by  Kiilz,  has 
been  proved  to  be  glucose,  and  is  present  in  the  liver  during  life  to 
the  amount  of  from  0.2  to  0.5  per  cent.  (Bernard,  Seegen). 

After  some  knowledge  on  these  subjects  had  been  gained  through  earlier 
investigations,  Claude  Bernard,  late  in  the  forties,  proved  the  constant  presence 
of  sugar  in  the  blood,  independently  of  the  kind  of  food  taken,  and  showed  that 
it  must  be  looked  for  shortly  after  the  blood  is  obtained,  as  it  soon  decomposes. 
He  showed  that  the  sugar  of  the  blood  is  formed  in  the  liver,  which  always  con- 
tains some,  and  that  a  piece  of  liver  from  which  the  sugar  has  been  removed 
by  washing  soon  again  becomes  sacchariferous.  He  explained  this  by  the 
continued  activity  of  the  diastatic  ferment  constantly  producing  sugar,  which 
increases  when  not  removed  by  the  circulation.  When  Pavy  afterward  con- 
sidered this  process  to  take  place  exclusively  after  death,  Bernard  (as  Dalton, 
Seegen,  and  others  have  done  after  him)  showed  that  the  liver  during  life  also 
contained  sugar,  the  quantity  of  which  he  (by  somewhat  too  low  an  estimate) 
placed  at  0.24  per  cent. 

*Arthus  and  Hubner,  however,  have  shown  that  a  solution  of  fluorin  (l  :  loo), 
which  destroys  cellular  life,  does  not  prevent  the  fern  ation  of  glucose  in  pieces  of  liver. 
Schwiening  believes  that  the  proteids  play  some  special  role  in  the  formation  of  glucose 
in  the  liver. 


METABOLISM    AND    NUTRITIVE    NEEDS.  161 

Nearly  ten  years  afterward  Claude  Bernard  and  Hensen  discovered  the 
glycogen,  determined  its  nature,  and  proved  that  it  could  be  formed  both  from 
proteids  and  from  carbohydrates.  Bernard  showed  also  that,  if  the  liver  is 
separated  from  the  circulation,  the  sugar  disappears  from  the  blood — a  fact  after- 
ward corroborated  by  Bock  and  Hoffmann  and  by  v.  Mering.  Bernard  found, 
moreover,  that  the  veins  issuing  from  the  liver  and  the  inferior  vena  cava 
usually  contain  more  sugar  than  the  portal  vein.  On  finding  more  sugar  in 
the  inferior  vena  cava  than  in  the  carotid  artery,  he  first  concluded  that  the 
sugar  is  consumed  in  the  lungs,  but,  always  ready  to  be  corrected  by  facts,  he, 
after  Chauveau's  investigations,  and  after  having  himself  found  more  sugar  in 
the  arteries  than  in  the  collateral  veins,  expressed  the  opinion  that  this  con- 
sumption takes  place  in  the  tissues  of  the  whole  organism.  Bernard  showed 
that  the  sugar  of  the  blood  usually  undergoes  only  slight  variations  in  quantity, 
that  it  is  somewhat  increased  after  generous  meals,  that  it  gradually  diminishes 
on  starvation  and  in  the  febrile  state,  and  that  it  disappears  from  the  blood 
outside  the  organism  in  about  twenty-four  hours.  Finally,  Bernard  found 
glycosuria  after  lesions  of  the  brain  in  the  floor  of  the  fourth  ventricle,  made 
investigations  concerning  hyperglycemia  in  diabetes,  and  showed  that  glyco-, 
suria  in  the  dog  begins  when  the  sugar  in  the  blood  reaches  from  0.25  to  0.30 
per  cent. 

At  about  the  same  time  Lehmann  found  traces  of  sugar  in  the  portal  vein, 
and  determinable  quantities  of  it  in  the  veins  issuing  from  the  liver  (horse). 

C.  Schmidt,  in  1850,  without  a  knowledge  of  the  results  of  Bernard's  inves- 
tigations, found  sugar  in  the  blood  of  cows,  dogs,  and  cats. 

Chauveau,  partly  alone  and  partly  in  conjunction  with  Kaufmann,  has, 
since  1856,  contributed  more  than  any  one  else  to  the  confirmation  of  Bernard's 
theories.  After  extensive  and  numerous  experiments  he  came  to  the  conclu- 
sion that  the  sugar  in  the  blood  is  derived  from  the  liver,  that  it  is  always  pres- 
ent, and  even  after  long-continued  starvation  does  not  entirely  disappear  ;  that 
the  arteries  contain  more  sugar  than  the  collateral  veins,  and  that  all  divisions 
of  the  circulatory  system  contain  about  the  same  amount,  except  the  veins 
issuing  from  the  liver  and  the  inferior  vena  cava,  which  are  more  saccharifer- 
ous,  and  the  portal  vein,  which  (except  after  the  ingestion  of  large  amounts 
of  carbohydrates)  is  less  sacchariferous  than  other  vessels. 

Subsequently,  Bohm  and  Hoffmann,  Bock  and  Hoffmann,  Bleile,  Kiilz, 
Lusk,  v.  Mering,  Ewald,  Otto,  Barral,  Lepine,  and  others  made  investigations 
which  have  corroborated  Bernard's  results. 

Pavy,  one  of  Bernard's  own  disciples,  began  at  the  close  of  the  fifties  his 
opposition  to  this  greatest  of  French  experimenters.  Pavy  found  that  the 
blood  from  the  right  heart  of  a  living  dog  contained  much  less  sugar  than  after 
death — an  observation  that  is  certainly  correct,  and  is  dependent  on  the  fact 
that  when  the  circulation  gradually  ceases,  the  districts  next  to  the  liver,  where 
the  formation  of  sugar  continues  even  some  time  after  death,  become  more 
sacchariferous.  Pavy  found  also  that  bits  of  liver  obtained  from  living  animals 
and  thrown  into  boiling  water  or  subjected  to  freezing  contained  only  small 
quantities  of  sugar,  while,  when  exposed  to  ordinary  temperature,  they  con- 
tained much  larger  quantities.     This  is  also  true,  partly,  perhaps,  because  the 


1 82  DIABETES    MELLITUS    AND    GLYCOSURIA. 

liver-cells  of  living  animals  produce,  and  the  dead  liver-cells  do  not  produce, 
sugar,  and  partly  because  excessive  temperatures  diminish  the  influence  of  the 
diastatic  ferment.  Pavy  concluded  from  these  observations  that  the  production 
of  sugar  in  the  liver  is  aportmortem  phenomenon,  and  that  in  life  the  sugar  passes 
through  the  liver  only  under  pathologic  conditions,  as  in  diabetes  or  after  cer- 
tain lesions,  probably  in  consequence  of  a  vasomotor  neurosis  which  leads  to 
congestion  of  the  liver  with  blood  that  has  not  entirely  lost  its  arterial  qualities. 
This  sugar,  then,  may  come  from  the  glucose  formed  normally  by  ingested 
carbohydrates  or  from  the  glycogen,  which  customarily  produces  fat.  Even 
Pavy  has  been  forced  to  acknowledge  the  presence  of  sugar  in  the  blood  under 
ordinary  conditions,  but  he  believes  it  to  be  there  only  in  insignificant  traces  and 
for  no  physiologic  purpose,  admitted,  as  it  were,  by  some  defect  in  the  func- 
tions of  the  liver,  escaping  again  through  the  kidneys  as  a  trace  of  sugar  in 
the  urine.  Pavy's  views  have  now  only  historic  and  personal  interest,  and  are 
strenuously  opposed  even  in  Great  Britain  {e.  g.,  by  Dr.  Noel  Paton  [1898]  ). 
For  many  years,  however,  they  exercised  considerable  influence.  Among 
Pavy's  adherents  were  Schiff,  Meissner,  Ritter,  MacDonnell,  and  (as  late  as 
1876)  Lussanna. 

Seegen  also  was  at  first  an  adherent  of  this  view.  Then  having  found 
(with  Kratschmer)  that  diastatic  ferment  in  saliva  and  in  the  pancreatic  juice 
does  not  change  glycogen  into  glucose,  but  into  another  saccharid,  which  Mus- 
culus  and  v.  Mering  showed  to  be  maltose,  and  finding  in  the  liver  no  other 
substance  capable  of  saccharifying  the  glycogen,  he  began  to  doubt  that  it  was 
the  source  of  the  glucose.  In  a  series  of  experiments  he  sought  and  believed 
that  he  had  found  that  the  glucose  must  be  derived  from  other  substances  than 
glycogen.  He  found  the  glucose  to  increase  in  bits  of  liver  before  the  glycogen 
began  to  decrease.  Investigations  on  this  subject,  however,  by  Bohm  and 
Hoffmann,  Girard,  Chittenden  and  Lambert,  Bial,  Butte,  and  Montuori  have  not 
corroborated  Seegen's  results.  Seegen,  by  various  experiments,  for  which  I 
must  refer  to  his  own  works,  believed  also  that  he  had  proved  the  formation  of 
glucose  in  the  liver  from  peptone,  a  process  which  Lupine  considers  to  take 
place  throughout  the  whole  organism.  Hofmeister,  Chittenden,  Lambert, 
Neumeister,  and  Bial  have  also  on  this  point  arrayed  themselves  against  Seegen, 
and  arrived  at  other  conclusions.  Seegen  believed,  further,  that  he  had  found 
in  70  cases  the  blood  of  the  hepatic  veins  always  more  sacchariferous  than  the 
blood  of  the  portal  vein,  and  he  somewhat  irrationally  considered  this  a  proof 
of  the  correctness  of  his  views.  In  this  also  he  has  powerful  opponents;  both 
Bernard's  and  v.  Mering's  observations  tend  to  show  that  after  the  ingestion 
of  large  amounts  of  carbohydrates  the  portal  vein  may  contain  a  much  higher 
percentage  (up  to  0.4  percent.)  than  the  hepatic  veins  or  the  inferior  vena 
cava. 

It  must  be  remembered  that  we  here  have  usually  to  do  with  small  differ- 
ences. Max  Mosse  found  0.107  per  cent,  in  the  hepatic  veins  and  0.093  per 
cent,  in  the  femoral  artery,  which,  according  to  Seegen,  contains  only  slightly 
more  than  the  portal  vein.  Mosse  and  others  are  in  all  probability  right  when 
they  maintain  that  the  high  percentage  of  glucose  sometimes  found  in  the 
blood  just  coming  from  the  liver  is  partly  due  to  the  sufferings  of  the  animal 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 83 

during  the  experiment.  Seegen  finally  remarks  that,  while  glycogen  is  driven 
out  of  the  liver  by  starvation,  the  sugar  of  the  blood  remains  in  unchanged 
quantity.  This  is  decidedly  wrong.  Claude  Bernard,  Bohm  and  Hoffmann, 
and  Otto  all  have  shown  that  prolonged  starvation  does  decrease,  though 
slowly,  the  sugar  of  the  blood  ;  and,  on  the  other  hand,  Kiilz  has  shown  that 
even  starvation  for  twenty  days  does  not  fully  free  either  liver  or  muscles  from 
glycogen.  Seegen,  however,  is  determined  to  adhere  to  his  opinion  that  gly- 
cogen does  not  form  glucose,  but  fat,  and  that  the  liver  for  purposes  of  vital 
energy  produces  glucose  from  fat  and  proteids.  At  the  same  time  that  Seegen 
denies  the  formation  of  glucose  from  the  glycogen  of  the  liver  he  accepts  such 
a  formation  from  the  glycogen  of  the  muscles.  This  surely  appears  a  rather 
far-fetched  theory,  and  the  presumed  facts  on  which  it  is  based  have  not  been 
established,  nor  would  they  necessarily  lead  to  Seegen's  conclusions  even  if 
they  were  so ;  but,  according  to  the  strongest  evidence,  some  of  them  are  false. 
Naturalists  will  not,  without  convincing  proofs,  believe  that  nature  should  form 
exclusively  fat  from  carbohydrates,  and  at  the  same  time  and  in  the  same 
organ  should  form  carbohydrates  from  fat ;  and  even  those  who  believe  that 
fat  may  form  glucose  under  certain  circumstances  are  far  from  accepting 
Seegen's  views,  which  now,  like  Pavy's,  may  be  considered  to  be  a  matter  of 
history. 

We  now  have  acquired  a  right  to  consider  the  hver  as  the  main 
sugar-producing  organ  of  the  body,  and  to  look  upon  the  sugar  of 
the  Hver,  which  is  identical  with  the  sugar  of  the  blood,  as  derived 
from  the  glycogen.  We  have  seen  that  the  sugar  of  the  blood 
usually  is  most  abundant  in  the  vessels  leaving  the  liver,  and  that 
it  decreases  and  disappears  if  the  liver  is  cut  off  from  the  circula- 
tion. We  have  seen  also  that,  when  the  sugar  increases  in  portions 
of  liver,  there  is  a  corresponding  decrease  in  glycogen.  This  fact 
may  be  demonstrated  experimentally  even  during  life  by  irritation 
of  the  celiac  plexus  or  the  sympathetic  nerves  of  the  liver,  which 
produces  an  immediate  increase  in  the  amount  of  sugar  with  a 
corresponding  decrease  in  the  amount  of  glycogen  (Chauveau, 
Cavazzani  and  Butte,  Morat  and  Dufour).  Marcuse  has  lately 
shown  that  the  diabetes  that  is  constantly  caused  also  in  frogs  by 
extirpation  of  the  pancreas  is  prevented  by  previous  extirpation  of 
the  liver.  Finally,  we  know  that  phloridzin,  which  causes  the  sugar 
of  the  blood  to  pass  into  the  urine  without  hyperglycemia  in  con- 
sequence of  changes  in  the  kidneys,  and  causes  a  constant  and  rapid 
reproduction  of  glucose,  decreases  the  glycogen,  and  that  diabetes 
following  the  extirpation  of  the  pancreas,  with  the  consequent  enor- 
mous losses  of  glucose,  has  the  same  effect. 


184  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Generally,  glycogen  is  believed  to  represent  fixed,  stored-up 
potential  energy,  which,  whenever  it  is  found,  may  be  changed  into 
glucose,  representing  potential  energy  in  solution  ready  to  be  trans- 
formed into  vital  force. 

So  far,  so  good  ;  but  what  about  the  important  questions  that 
next  present  themselves  ? 

Does  all  transformation  into  vital  force  necessarily  pass  through 
the  molecular  structure  of  glucose,  or  may  proteids  and  fat  be 
used  unchanged  for  this  purpose  ? 

Can  glucose  be  formed  from  proteids  anywhere  else  than  in  the 
liver  ? 

Can  glucose  be  formed  at  all  from  fat  ? 

Can  carbohydrates  and,  perhaps,  fat  contribute  to  a  possible  syn- 
thetic formation  of  proteids  ? 

Where  and  how  are  the  molecules  of  fat  attacked  and  disinte- 
grated ? 

It  appears  to  me,  unfortunately  unable  to  form  an  opinion  on 
these  subjects,  but,  from  the  researches  of  others,  that  we  can  at 
present  not  give  much  more  definitive  answers  to  these  questions 
than  we  could  in  the  beginning  of  the  last  decad  of  the  nineteenth 
century. 

Chauveau  has  recently  formulated  his  own  conclusions  from 
extensive  researches  on  the  transformation  of  force  within  the  or- 
ganism. These  conclusions,  in  a  somewhat  abbreviated  form,  are 
as  follows  : 

1.  All  vital  force  within  the  organism  is  produced  by  oxidation. 

2.  The  potential  energy  is  always  in  the  ultimate  stage  repre- 
sented by  carbohydrates. 

3.  During  starvation  carbohydrates  are  constantly  formed  also 
by  a  rudimentary  oxidation  of  fats. 

4.  Oxidation  of  proteids  never  directly  contributes  to  the  pro- 
duction of  vital  force  ;  or,  in  other  words,  mechanical  work  does 
not  increase  the  amount  of  nitrogen  in  the  urine. 

Unfortunately,  there  are  still  various  opinions  with  regard  to 
each  of  these  conclusions.  Munk,  Zuntz,  and  others  think  it  still 
doubtful  that  all  vital  force  is  produced  by  oxidation.  We  know, 
especially  from  the  researches  of  Zuntz,  that  mechanical  work  in 
some  way  may  be   sustained  by  fat  and  by  proteids,  as  well  as  by 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 85 

carbohydrates,  and  Newton  Heyneman's  experiments  prove  also, 
by  the  figures  of  the  respiratory  quotient,  that  the  kind  of  food 
chiefly  ingested,  be  it  proteids,  fat,  or  carbohydrates,  is  also  chiefly 
used  for  the  production  of  mechanical  force. 

The  power  of  the  organism  to  produce  carbohydrates  from  fats  is 
exceedingly  doubtful.  Something  may  be  said  in  favor  of  the  exist- 
ence of  such  a  power,  but  it  seems  to  me  that  still  much  more  may 
be  said  against  it.  The  chief  reason — apart  from  the  much  opposed 
results  of  Seegen's  experiments — for  believing  in  the  formation 
of  glycogen  or  glucose  from  fats  depends  on  the  highly  uncertain 
theory  that  muscles  can  not  use  fats  as  fuel  for  their  work.  It  has 
been  demonstrated  that  with  a  scanty  supply  of  carbohydrates  the 
quantity  of  proteids  and  carbohydrates  consumed  does  not  always 
cover  the  expense  of  the  mechanical  work  performed.  The  for- 
mation of  carbohydrates  from  fats  in  vegetable  cells  constitutes 
absolutely  no  reason  for  admitting  such  a  formation  in  animal  cells. 
Any  one  who  has  at  all  occupied  himself  with  the  physiology  of 
plants  knows  what  an  enormous  metabolic  difference  there  is  be- 
tween animals  and  plants.  The  clinician,  who  constantly  finds  that 
he  may  increase  the  butter  in  the  food  of  his  diabetic  patients  to 
any  ingestible  quantity  in  any  stage  of  diabetes  and  under  any  diet, 
without  any  perceptible  increase  of  the  amount  of  glucose  in  the 
urine,  will  have  strong  doubts  as  to  the  formation  of  carbohydrates 
from  fats  even  with  a  deficient  supply  of  carbohydrates  ;  and,  how- 
ever much  it  may  be  repeated  from  some  quarters  that  the  sugar 
of  the  blood  remains  at  par  during  feeding  with  fats  alone,  Seegen's* 
own  figures  show  that  the  sugar  of  the  blood,  after  having  dimin- 
ished during  starvation  continues  to  do  so  during  subsequent  feeding 
exclusively  on  fats.  Von  Mering,  Moritz  and  Praussnitz,  Cremer 
and  Ritter,  and  now  (1898)  Kumagawa  and  Miura  alike  consider 
that  during  phloridzin-poisoning,  with  its  enormous  loss  of  glucose, 
fats  do  not  give  rise  to  carbohydrates. 

Chauveau  has  been  led  to  his  conclusions  as  to  the  ability  of  the  organism 
to  produce  carbohydrates  from  fats  chiefly  by  his  own  and  by  Regnault's  and 

*  Among  authorities  now  Hving,  so  far  as  I  know,  only  Seegen,  v.  Noorden,  Bunge, 
Chauveau  and  Kaufmann,  and  Weiss  accept  the  formation  of  carbohydrates  from  fats  in 
man. 

13 


1 86  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Reiset's  investigations  on  the  marmot.  This  animal,  when  subjected  to  star- 
vation in  summer,  dies  after  the  loss  of  between  95  per  cent,  and  97  per  cent. 
of  its  fat,  and  then  has  scarcely  any  carbohydrate  at  all  left  in  liver,  muscles, 
or  blood.  After  hibernation  the  marmot  has  used  up  its  fat,  but  the  blood  still 
.  contains  glucose  and  the  liver  and  muscles  contain  glycogen.  Chauveau 
asks  how  this  could  be,  after  such  a  time  of  continued  abstinence  from  food, 
with  considerable  expenditure  for  heat  and  circulation,  if  the  carbohydrates 
(glycogen  and  glucose)  had  not  been  formed  from  fat.  Then  Regnault  and 
Reiset  had  observed  that  the  marmot  may,  during  its  sleep  in  hibernation, 
increase  in  weight,  and  that  it  consumes  considerably  more  oxygen  than  it 
expires  in  carbonic  acid,  and  Chauveau  thinks  that  the  fat  has  been  changed 
into  glucose  by  oxidation  according  to  the  following  equation  : 

2C57HJ10O6  +  670,  =  i6CgHi,06  +  18CO2  +  I4H,0. 
Stearin.  Glucose.        Carbonic     Water. 

Acid. 

The  question  whether  proteids  directly  produce  vital  force  is  not 
to  be  answered  at  present.  Voit,  Brietske,  Fick  and  Wislicenus, 
and  others  found  no  increase  in  the  nitrogen  of  the  urine  after 
mechanical  work.  Pavy,  Flint,  Parkes,  Argutinsky,  Oppenheim, 
and  others  arrived  at  opposite  results,  and  Zuntz,  too,  after  his 
beautiful  researches,  has  formed  the  opinion  that  proteids  (and  fats) 
may  directly  contribute  to  the  formation  of  vital  force. 

Finally,  it  is  not  impossible  that  a  part  of  the  proteids  so  utilized 
is  derived  from  carbohydrates.  Pfliiger,  Schenk,  and  others  admit 
a  synthetic  formation  of  proteids,  as  a  station  on  the  way  to  the 
final  production  of  vital  force,  to  which  formation  carbohydrates 
may  contribute  part  of  the  nonnitrogenous  constituents.  So  long 
as  we  do  not  know  more  than  we  do  at  present  of  the  fate  of  the 
fats,  we  can  not  absolutely  deny  its  participation  in  such  a  synthesis 
of  proteids. 

Until  further  information  is  forthcoming  it  must  be  admitted  that 
proteids  may  form  proteids,  fats,  and  carbohydrates,  that  carbo- 
hydrates may  form  carbohydrates  and  fats,  but  that  fats  are  not 
positively  known  to  form  anything  but  fat.  On  the  other  hand,  we 
have  no  right  to  deny  positively  the  formation  under  some  circum- 
stances of  carbohydrates  from  fat ;  still  less  have  we  a  right  to 
deny  the  synthesis  of  proteids,  in  which  both  carbohydrates  and 
fats  may  participate. 

The  sugar  of  the  blood  is  proved  to  be  glucose,  and  is  found  in 
the  serum. 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 87 

The  quantity  of  sugar  in  the  blood  varies  normally  from 
0. 10  to  0.15  per  cent.,  and  it  may,  perhaps,  sometimes  slightly 
exceed  these  limits  in  either  direction.  The  veins  contain  some- 
what less  than  the  collateral  arteries.  The  portal  vein,  except  after 
the  ingestion  of  large  amounts  of  carbohydrate,  contains  less  and 
the  hepatic  veins  contain  more  than  do  other  vascular  areas. 
Unlike  the  glycogen  of  the  liver,  which  varies  enormously  under 
different  dietetic  conditions,  the  amount  of  sugar  in  the  blood  nor- 
mally undergoes  but  comparatively  shght  variations.  It  increases 
somewhat  after  the  ingestion  of  large  amounts  of  carbohydrate 
(Claude  Bernard,  v.  Mering)  and  after  copious  hemorrhage  (Edel, 
Schenk),  and  decreases  during  continued  starvation  (Bernard, 
Bock  and  Hoffmann,  Otto,  Seegen,  Chauveau),  during  the  febrile 
state,  after  extirpation  of  the  liver,  and  as  a  result  of  poisoning 
with  phloridzin.  The  quantity  of  sugar  in  the  blood  is  about 
half  of  the  quantity  of  fibrin,  and  the  amount  is  not  small  consid- 
ering that  the  sugar  is  being  constantly  produced  and  constantly 
consumed.  Seegen  calculates  that  a  human  being  produces  and 
consumes  about  lo  grams  of  glucose  per  kilogram  of  bodily 
weight  in  twenty-four  hours.  A  German,  Anglo-Saxon,  or  Scan- 
dinavian of  ordinary  size  thus  manufactures  and  uses  up  between 
700  and  800  grams. 

The  sugar  of  the  blood  is  consumed  in  the  different  tissues  of 
the  organism,  but  chiefly  in  the  muscles  ;  and  by  its  oxidation  into 
carbonic  acid  and  water  it  forms  the  organism's  largest,  but  prob- 
ably not  its  only,  source  of  vital  power. 

The  sugar  of  the  blood  causes  reduction  of  copper-  and  bismuth-solutions ; 
undergoes  fermentation,  with  the  generation  of  alcohol,  carbonic  acid,  etc. ; 
forms  with  potassium  a  combination,  out  of  which  it  may  be  driven  by  car- 
bonic acid  (Seegen,  Ludwig,  Abeles) ;  deflects  the  ray  of  polarized  light  to  the 
right  (Ewald) ;  and  yields  glycosazone  with  phenyl-hydrazin-chlorate  and 
sodium  acetate  (Pickhardt).  Thus,  there  is  no  doubt  that  it  is  glucose.  To 
this  rule  there  may,  however,  be  rare  exceptions ;  it  seems  probable  that  in 
cases  in  which  the  sugar  in  the  urine  is  another  saccharid — .?.  ^.,  levulose — 
the  sugar  of  the  blood  is  also  constituted  by  this  saccharid. 

Otto  proved  the  sugar  of  the  blood  to  be  contained  in  the  serum  by  intro- 
ducing in  Hoppe-Seyler's  equation  for  the  valuation  of  blood-corpuscles  from 
the  quantity  of  plasma  and  fibrin  (in  two  cases)  the  figures  of  the  sugar  instead 
of  the  figures  of  the  fibrin,  arriving  at  nearly  the  same  figures  as  Hoppe- 
Seyler's  equation  gave.     Calculating  with  the  aid  of  Hoppe-Seyler's  equation, 


i88 


DIABETES    MELLITUS    AND    GLYCOSURIA. 


he  found  in  one  case  64.65  per  cent,  of  plasma  and  35.35  per  cent,  of  red 
blood-corpuscles ;  and  with  his  own  equation  he  found  the  corresponding 
figures  to  be  64.29  and  35.71.  In  a  second  case  the  analogous  figures  were 
67.88  and  32.12,  and  67.96  and  32.04.  The  figures  representing  fibrin  and 
sugar  were  as  follows  : 


Cases. 

Blood. 

Plasma. 

Fibrin. 

Sugar. 

Fibrin. 

Sugar. 

I, 

0.205   psi'  cent. 

O.I  16  per  cent. 

0.317  per  cent. 

0.182  per  cent. 

2, 

0.311        " 

0.123 

0.458       " 

0.181 

Naunyn  states  the  normal  quantity  of  sugar  in  the  blood  as  about  o.i  per  cent. 
— rather  somewhat  below  (from  0.08  to  0.09)  than  above  this  figure  ;  Bernard 
found  between  0.09  and  0.117  per  cent. ;  Seegen,  between  0.12  and  0.19,  and 
as  an  average  in  ten  cases,  nearly  0.17  per  cent. ;  Otto,  nearly  0.12  per  cent. ; 
V.  Mering  (in  the  serum),  between  0.13  and  0.14  per  cent.  ;  Frerichs,  between 
0.12  and  0.30  (!!!)  per  cent.  All  of  these  figures  refer  to  man.  In  the  rab- 
bit Otto  found  between  0.09  and  o.ii  per  cent.;  Barral,  in  the  dog,  between 
0.08  and  0.17  per  cent.  ;  Otto,  in  the  dog,  o.ii  per  cent.  The  highest  of  these 
figures  include  not  only  the  sugar,  but  all  reducing-substances  in  the  blood 
(kreatinin,  uric  acid,  etc.),  and  thus  represent  too  high  a  value  for  the  glucose. 
Otto  corrected  this  error,  which,  besides,  shows  a  wrong  relation  between  the 
quantity  of  sugar  in  the  arteries  and  that  in  the  veins,  the  reducing,  nonsac- 
charine  substances  being  present  in  greater  quantity  in  the  veins  than  in  the 
arteries.  Otto  found  in  the  dog,  in  blood  from  the  femoral  artery,  a  reduction 
before  fermentation  of  0.160  per  cent.,  and  after  fermentation  of  0.034  per  cent., 
the  amount  of  glucose  thus  equaling  0.126  per  cent. ;  in  blood  from  the  femoral 
vein  of  the  same  dog  a  reduction  before  fermentation  of  0.158  per  cent.,  and 
after  fermentation  of  0.039  P^i"  cent.,  the  amount  of  glucose  thus  equaling 
0.1 19  per  cent.  (The  blood  was  taken  simultaneously  from  both  vessels.) 
After  hemorrhage  the  reduction  is  increased.  Otto  considered  this  to  be  an 
effect  of  the  increase  of  nonsaccharine  reducing-substances.  Bernard  had 
mentioned  this  increase  as  due  to  the  presence  of  an  increased  amount  of 
glucose,  and  Schenk,*  in  opposition  to  Otto,  maintains  that  the  whole  increase 
is  due  to  the  presence  of  glucose. 

The  excess  of  glucose  in  the  arteries  over  that  in  the  veins  is  small ;  accord- 
ing to  Otto,  the  proportion  is  12  :  11;  according  to  Barral,  100  :  92.7.  As  already 
mentioned,  the  hepatic  veins  generally  contain  most,  and  the  portal  vein  least 
sugar  of  all  vessels.  The  great  difference,  however,  that  has  so  often  been 
found  is  i7i  part  the  effect  of  a  marked  increase  in  the  production  of  sugar 
in  the  liver  from  nervous  causes  during  the  experiment.  Mosse,  who  arranged 
his  experiments  with  a  view  to  the  elimination  of  this  influence,  found  only 


*"  Pfliiger's  Archiv,"  1894. 


METABOLISM    AND    NUTRITIVE    NEEDS. 


189 


0.107  per  cent,  of  glucose  in  the  hepatic  veins;  the  portal  vein  rarely  contains 
less  than  0.08  or  0.09  per  cent.  After  the  ingestion  of  large  amounts  of  carbo- 
hydrate the  portal  vein  may  contain  as  much  as  0.4  per  cent.,  and  much  more 
than  the  hepatic  veins  (v.  Mering). 

The  accompanying  table,  showing  the  results  of  Seegen's  experiments,  illus- 
trates the  influence  of  diet  on  the  amount  of  glycogen  in  the  liver  and  the 
amount  of  glucose  in  the  blood.  The  figures  representing  the  amount  of 
glucose  in  the  hepatic  veins  probably  are  much  too  high,  from  the  influence  of 
the  experiment  on  the  nerves  ;  and  all  the  figures  relating  to  glucose  in  reality 
represent  both  glucose  and  other  reducing-substances.  Nevertheless,  I  con- 
sider the  relations  of  this  conscientious  experimenter's  figures  to  be  of  great 
value.  The  observations  were  made  upon  dogs  that  had  been  subjected  to 
starvation  for  eight  days,  and  were  then  fed  exclusively  on  one  of  the  several 
kinds  of  food  named.  I  would  call  attention  to  the  most  important  fact  that 
both  glucose  and  glycogen  reach  their  lowest  figures  when  the  period  of  pre- 
liminary starvation  is  followed  by  a  period  in  which  the  only  food  is  fat. 


Food. 


Glucose. 


Carotid. 


Portal  Vein. 


Hepatic  Vein. 


Glycogen 

IN 

Liver. 


None, 

Fat, 

Muscle, 

Starch,     .    

Cane-sugar,     .... 
Cane-sugar  and   dex- 
trin,       


0.157  per  cent. 
0.128       " 

0-I55  " 
0.165  " 
0.165       " 

0.176       " 


o.  147  per  cent. 
0.I14       " 
o.  141       " 
0.147       " 
0.186       " 

0.258   " 


0.269  P^""  cent. 
0.217   " 
0.281   " 
0.261   " 
0.265   " 

0.327       <' 


1.67  per  cent. 
0.93       " 

3-7 

6.0         " 

9.4 


Chauveau  and  Kaufmann,  in  1886,  brought  to  light  important  facts  in  con- 
nection with  the  consumption  of  glucose  in  the  muscles.  They  determined  the 
amount  ,of  both  carbonic  acid  and  glucose  in  the  blood  from  the  masseter 
muscle  and  from  the  parotid  gland,  having  previously  made  a  corresponding 
analysis  of  the  blood  in  the  carotid.  This  artery  supplies  the  muscle  and 
the  gland  with  about  the  same  amount  of  blood,  which  in  both  is  about  three 
times  as  large  during  functional  activity  as  during  repose.  During  functional 
activity  the  muscle  consumed  about  5^  times  as  much  glucose  as  the  gland 
and  produced  about  five  times  as  much  carbonic  acid.  The  muscle  in  exercise 
produced  about  3^  times  as  much  carbonic  acid  as  in  repose,  and  also  con- 
sumed about  3>^  times  as  much  glucose.  With  the  gland,  the  figures  during 
functional  activity  and  in  repose  were  as  87  :  60  with  regard  to  the  production 
of  carbonic  acid,  and  as  90  ;  70  with  regard  to  the  consumption  of  glucose. 

Quinquaud  found  from  0.12  to  0.15  per  cent,  of  glucose  in  the  femoral  vein 
before,  but  only  0.07  per  cent,  after  strong  faradization. 


As  soon  as  the  sugar  in   the  blood  reaches  a  certain  amount, 
which  Claude  Bernard  found  to  be  about  0.25  per  cent,  in  the  dog, 


IQO  DIABETES    MELLITUS    AND    GLYCOSURIA. 

it  begins  to  pass  over  into  the  urine.  Lepine,  immediately  after  the 
beginning  of  the  glycosuria  in  diabetic  dogs  (following  extirpation 
of  the  pancreas),  found  between  0.19  and  0.24  per  cent,  of  glucose 
in  the  blood.  Seegen's  figures  indicate  that  glycosuria  in  man  may 
exist  with  less  glycemia  than  0.20  per  cent.  Still,  there  seems  to 
be  a  certain  interval  between  the  ordinary  glycemia,  which  only 
rarely  exceeds  0.15  per  cent.,  and  the  decided  hyperglycemia,  in 
connection  with  which  glycosuria  begins.  Thus,  we  find  glyco- 
suria often  absent  in  states  that  bring  about  hyperglycemia — £■  g-, 
asphyxia.  Carcinoma  is  usually  (Freund),  though  not  constantly 
(Matrai),  attended  with  hyperglycemia,  but  is  often  found  without 
glycosuria.  In  cases  of  simple  glycosuria  only  the  highest  degrees 
of  glycemia  give  rise  to  glycosuria,  which  appears  for  only  a  short 
part  of  the  day  some  time  after  meals.  In  cases  of  diabetes  there 
is  always  hyperglycemia  in  the  severe  and  often  in  the  light  stage. 
It  rarely  exceeds  0.4  per  cent.,  but  much  higher  figures  are  occa- 
sionally reached.  Pavy  found  0.57  and  Hoppe-Seyler  0.9  per 
cent,  of  glucose  in  the  blood.  Investigations  have  proved  that 
the  glycosuria  bears  no  fixed  relation  to  hyperglycemia  (Seegen, 
Lepine,  and  others).  Seegen  found  3.8  per  cent,  of  sugar  in  the 
urine  and  0.182  per  cent,  in  the  blood  ;  and  afterward,  in  the  same 
(mild)  case,  0.6  per  cent,  in  the  urine  and  o.  181  per  cent,  in  the 
blood.  In  a  severe  case  during  the  observance  of  a  strict  diet  he 
found  0.6  per  cent,  in  the  urine  and  0.19  per  cent,  in  the  blood. 
We  thus  see  that  the  hyperglycemia,  even  with  considerable  gly- 
cosuria, may  be  quite  moderate.  Still,  the  hyperglycemia  consti- 
tutes the  real  '^  nocens'' — the  sugar  in  the  urine,  which  alone  we 
are  generally  able  to  observe,  is  of  small  account.  A  moderate 
hyperglycemia,  however,  is  certainly  capable  of  only  a  moderate 
noxious  influence.  We  are  terrified  on  finding  a  glycosuria  of  3.8 
per  cent,  in  a  patient,  but  should  be  much  less  alarmed  if  told  at 
the  same  time  that  it  resulted  from  a  hyperglycemia  of  only  0.18 
per  cent.  Every  one  understands  at  once  that  if  it  is  normal  for 
the  blood  to  contain  0.12  per  cent.,  or  even  0.15  per  cent,  of  glu- 
cose, it  does  not  constitute  a  very  great  danger  for  it  to  contain 
0.18  per  cent,  of  glucose. 

I  now  arrive  at  that  much-discussed  question  whether  hypergly- 
cemia and  glycosuria — i.  e.,  diabetes   mellitus — arise  from  an   in- 


METABOLISM    AND    NUTRITIVE    NEEDS.  I9I 

creased  production  or  from  a  decreased  consumption  of  sugar,  or 
from  both  of  these  causes. 

The  first  essential  difference  in  metabolism  between  the  normal 
and  the  diabetic  individual  is  met  with  in  the  liver,  which  exhibits 
a  decreased  capability  of  storing  glycogen.  The  opinion  is  held 
by  many  that  this  deficiency  of  forming  glycogen — which  may 
afterward  be  used  for  producing  fat,  or,  in  case  of  need,  may  be  left 
to  the  blood  as  glucose — is  the  immediate  cause  of  diabetes.  The 
liver  is  incapable  either  of  keeping  the  formed  glycogen  in  that 
state  or  of  transforming  enough  of  the  glucose  derived  from  the 
food  into  glycogen,  and  thus  it  produces  or  permits  too  large  quan- 
tities of  glucose  to  escape  into  the  circulation.  Claude  Bernard 
believed  the  increased  production  of  sugar  in  the  liver  to  be  a  result 
of  hyperemia  and  of  the  action  of  the  diastatic  ferment  in  the  blood 
in  attacking  the  glycogen  too  vigorously — ^^  V augmentation  de 
rapidite  de  la  circidation  du  foie  accrdit  la  glycemie." 

Others — e.  g.,  Zimmer — sought  to  find  the  root  of  the  evil  in  the 
muscles  and  in  an  impaired  consumption  of  the  sugar  of  the  blood. 
When  in  these  latter  days  it  was  discovered  that  extirpation  of  the 
pancreas  causes  diabetes,  and  that  extirpation  of  the  thyroid  gland 
causes  myxedema,  Brown-Sequard  formulated  the  theory  of  an 
"  internal "  secretion  of  the  glands  in  addition  to  that  which  had 
hitherto  alone  been  observed.  The  profession,  as  already  men- 
tioned, for  a  large  part  adopted  the  view  that  the  pamcreas,  through 
an  internal  secretion,  sends  into  the  blood  some  substance  necessary 
to  the  combustion  and  the  utilization  of  the  sugar. 

Claude  Bernard  was  familiar  with  this  "  glycolytic  ferment,"  or, 
as  Nommes  calls  it,  the  "glycolysine."  It  is  this  ferment  that 
drives  the  sugar  out  of  the  extravasated  blood  in  about  twenty- 
four  hours.  Bernard  used  acetic  acid,  carbolic  acid,  or  sodium 
sulphate  to  prevent  or  retard  this  disappearance,  Lepine  has  pro- 
posed as  a  unit  of  glycolytic  power  the  relative  quantity  of  sugar 
that  disappears  from  the  blood  in  one  hour  at  a  temperature  of  38° 
C.  (100.4°  F.).  The  normal  unit  is  about  twenty  per  cent,  of  the 
whole  amount.  According  to  Lepine  and  Barral,  the  glycolytic 
power — which  seems  to  be  subject  to  great  variations  within  the 
normal — is  quite  low  at  a  temperature  of  15°  C.  (66°  F.),  but  it 
increases  then  for  a  while  with  the  higher  temperature,  and  is  very 


192  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Strong  at  40°  C.  (104°  F.).  At  52°  C.  (125.6°  F.)  it  suddenly 
decreases,  and  is  annihilated  at  54°  C.  (129.2°  F.).  Lepine  and 
his  disciples  have  made  extensive  researches  upon  the  glycolytic 
ferment,  which,  according  to  that  observer,  is  partly,  but  not  ex- 
clusively, formed  in  the  pancreas,  and  is  delivered  to  the  blood  and 
the  lymph  ;  it  is,  further,  chiefly,  but  not  exclusively,  fixed  in  the 
Avhite  blood-corpuscles.  Spitzer  found  the  glycolysis  effected  both 
by  the  red  and  the  white  blood-corpuscles.  The  process  is  one  of 
oxidation,  oxygen  being  taken  up  and  carbonic  acid  produced  (Kraus, 
Spitzer).  Barral  found  that  oxygen  and  ozone  slightly  increase,  while 
rarefied  air,  carbonic  acid,  and  carbon  monoxid  diminish  the  glyco- 
lytic power.  Acidity  also  lessens  and  finally  annihilates  the  glyco- 
lytic power.  This  is  also  the  effect  of  antipyrin  (Lepine  and  Barral, 
Brouardel  and  Loye),  of  sodium  carbonate,  of  morphin,  and  of  vale- 
rian (Butte).  Colenbrander  made  the  observation  that  the  glyco- 
lysis is  destroyed  by  the  extract  of  leeches.  Curare  augments  it 
somewhat  (Butte).  The  glycolysis  is  about  as  energetic  after  as 
before  defibrination  (Dastre). 

Lepine  considers  that  there  is  a  certain  alternation  between  the 
"internal"  secretion  (of  the  glycolytic  ferment)  and  the  external 
secretion  (of  the  pancreatic  juice)  in  the  pancreas.  By  irritation  of 
the  peripheral  stump  of  the  pneumogastric  nerve  Lepine  caused 
increased  secretion  of  pancreatic  juice,  and  found  that  at  the  same 
time  the  blood  from  the  pancreatic  vein  had  almost  entirely  lost 
its  glycolytic  power,  which  afterward  returned,  when  the  external 
secretion  had  moderated. 

After  ligation  of  the  pancreatic  duct  the  glycolytic  ferment  in  the 
blood  is  increased,  probably  as  a  result  of  pressure  on  the  glandu- 
lar cells  in  consequence  of  stasis. 

In  cases  of  diabetes  the  glycolytic  ferment  in  the  blood  is 
markedly  diminished,  according  to  Lepine  and  many  others  ;  there- 
fore less  sugar  is  consumed  in  the  tissues,  and  hyperglycemia,  with 
its  various  consequences — /.  e.,  diabetes — arises. 

Lepine  and  Metroz  *  found  that  in  normal  blood — at  37°  C. 
(98.6°  F.) — the  sugar  had  decreased,  as  a  result  of  glycolysis, 
from  0.13  per  cent,  to  o.  10  per  cent.;   i.  e.,  the  blood  had  lost 

*  "  Compt.  Rend.,"  1893. 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 93 

23  per  cent,  of  its  sugar.  In  diabetic  blood  under  the  same 
circumstances  the  glycolysis  may  bring  down  the  sugar  from 
0.32  to  0.29  per  cent.,  and  the  loss  amounts  to  less  than  10  per 
cent.  Not  only  the  relative,  but  also  the  absolute,  loss  of  sugar  is 
smaller  in  diabetic  than  in  normal  blood  ;  but  relative  loss  is  the 
one  to  be  taken  into  consideration.  Lepine  and  Metroz  have  found 
that  a  liter  of  normal  blood  customarily  loses  in  the  course  of  an 
hour  about  0.20  gram  of  sugar,  but  that  an  addition  of  glucose  to 
this  same  blood  may  cause  the  loss,  under  otherwise  the  same  cir- 
cumstances, to  amount  to  0.60  gram. 

Lepine  observed  chyle  from  the  thoracic  duct  of  a  normal  dog 
injected  in  the  veins  of  a  diabetic  dog  diminish  for  a  short  time  the 
glycosuria.  Lepine  and  Barral,  by  adding  such  chyle  to  a  solution 
of  glucose  in  water,  also  produced  "glycolysis,"  with  loss  of  glu- 
cose. They  also  found  the  normal  difference  between  arterial  and 
venous  blood  decreased  in  diabetes.  By  driving  the  blood  through 
the  extirpated  kidney  of  a  dog  in  Jacoby's  apparatus  they  proved 
that  loss  of  sugar  takes  place  in  the  tissues  independently  of  ner- 
vous influences.*  For  the  details  of  the  extensive  researches  of 
Lepine  and  his  disciples  I  must  refer  to  his  own  treatises. 

Hedon  also,  by  a  series  of  investigations,  has  tried  to  establish  a 
defective  glycolysis  in  cases  of  diabetes  and  to  exclude  an  increased 
production  of  sugar  in  the  liver.  He  maintains  that  on  separating 
the  liver  from  the  circulation  the  sugar  disappears  (by  glycolysis) 
from  normal,  but  not  from  diabetic,  blood.  Minkowski  submits  that 
this  last  fact  may  depend  upon  an  abnormal  transformation  into 
glucose  of  the  glycogen  of  the  muscles.  For  other  results  of 
Hedon's  researches  also  I  must  refer  to  the  original  communica- 
tions. 

Several  experimenters,  and  especially  Minkowski,  have  come  to 
other  conclusions  than  those  of  Lepine.  Minkowski  found  the 
glycolysis  in  the  blood  of  a  diabetic  dog  to  be  quite  normal,  and  he 
was  not  able  to  reduce  the  glycosuria  by  injections  of  glycolytic 
ferment  or  of  pancreatic  extract ;  he  points  out  that  the  experiments 
with  Jacoby's  apparatus  do  not  exclude  postmortem  changes — 
Qui  z'ivra,  verra  ! 

*  Barral,  "  Sucre  du  Sang,"  Paris,  1890. 


194  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Lepine  also  mentions  a  '' pouvoir  saccliariferant''  of  the  blood. 
While  the  '' pouvoir  glycolytigue "  ceases  at  54°  C.  (129.2°  F.), 
the  saccharification,  which  is  effected  in  the  serum,  is  at  its  best  at 
from  56°  to  58°  C.  (132.8°  to  136.4°  F.),  and  gives  rise  to  the  pro- 
duction of  about  one  gram  of  sugar  to  the  kilogram  of  blood.  The 
material  for  this  production  of  glucose  is,  according  to  Lepine  {vide 
Seegen),  left  by  peptones.  The  '^ pouvoir  sacchariferant,"  like  the 
" potcvoir  glycolytigue,"  is  increased  by  acute,  but  reduced  by  slow, 
asphyxia. 

Lepine,  while  laying  the  greatest  stress  on  reduced  "  glycolysis  " 
and  diminished  consumption  of  sugar  as  a  cause  of  diabetes,  pru- 
dently does  not  deny  an  increased  production  of  glucose  as  an  addi- 
tional cause.  It  is  interesting  to  note  Kaufmann's  plea  *  for  the 
view  at  which  he  and  Chauveau  have  arrived  as  a  result  of  numerous 
experiments.  The  production  of  sugar  is,  according  to  Kaufmann, 
like  the  oxidation  in  the  lungs,  a  regulative  function  of  one  organ. 
The  consumption  of  sugar,  on  the  other  hand,  is  a  common  quality 
of  the  different  tissues,  which  consume  sugar  in  order  to  be  able  to 
perform  their  functions,  but  which  do  not  perform  their  functions 
for  the  purpose  of  consuming  sugar.  When  a  deviation  from  the 
normal  takes  place,  it  is  more  reasonable  to  look  for  the  cause  in  the 
organ  among  whose  functions  is  the  production  and  distribution  of 
sugar — i.  e.,  the  liver — than  in  those  organs  that  have  only  indirectly 
anything  to  do  with  the  sugar.  In  hibernating  animals,  in  spite  of 
their  comparatively  profound  muscular  repose,  one  does  not  find 
hyperglycemia  but  hypoglycemia,  and  only  when  they  return  to 
muscular  activity  does  the  sugar  in  the  blood  reach  its  full  amount. 
In  this  instance  production  is  seen  to  depend  on  consumption. 
Chauveau  and  Kaufmann,  in  1893,  demonstrated  the  fact  that  the 
sugar  increases  in  organs,  especially  in  muscles,  when  they  are 
occupied  in  their  functions.  By  administering  large  amounts  of 
glucose  or  by  injections  of  glucose  into  the  portal  vein  one  may 
induce  a  glycosuria  that  manifestly  has  nothing  to  do  with 
diminished  consumption,  but  with  the  overstraining  of  the  liver's 
capability  of  transforming  and  storing  glucose  in  the  form  of 
glycogen.     This  capability  is  reduced  in  cirrhosis  of  the  liver  ;  this 

*  "  Sem.  Med.,"  January  l6,  1895. 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 95 

is  the  cause  of  the  frequency  of  glycosuria  in  connection  with  that 
disease.  Kaufmann  further  calls  attention  to  Dastre's  view  that  in 
cases  of  asphyctic  glycosuria  the  asphyctic  blood  causes  an  abnor- 
mally large  production  of  sugar  in  the  Hver  by  stimulating  the 
organ  to  increased  activity.  In  the  course  of  glycosuria  due  to 
other  poisons  (curare,  morphin,  and  anesthetics  in  general)  there  is 
certainly  a  reduction  in  oxidation  and  in  consumption ;  but  the 
glycosuria  is  not  caused  by  this,  being  often  developed  during  the 
stage  of  excitement,  before  the  decrease  of  oxidation  and  consump- 
tion ;  under  these  conditions  also  the  glycosuria  results  from 
increased  production.  After  Bernard's  puncture,  with  the  develop- 
ment of  glycosuria  the  consumption  of  sugar  is  normal  (Chauveau). 
In  the  course  of  glycosuria  from  irritation  of  peripheral  nerves  the 
animals  are  much  excited  and  consumption  is  increased.  After 
section  of  the  spinal  cord  between  the  last  cervical  and  the  first 
dorsal  vertebra  Bernard  found  (after  a  transitory  hyperglycemia 
from  the  operation  per  se),  in  spite  of  the  lameness  and  reduced 
consumption,  no  hyperglycemia,  but  a  decided  hypoglycemia.  The 
lowered  temperature  in  cases  of  severe  diabetes  does  not  depend  on 
the  diabetes,  but  on  the  marasmus. 

Chauveau  and  Kaufmann  *  accept  a  combined  activity  of  the  liver 
and  the  pancreas  for  the  regulation  of  the  glucose — economy  of 
the  organism,  each  organ  having  an  inhibitory  and  a  stimulating 
nervous  center  influencing  its  secretion.  The  medulla  oblongata 
contains  a  stimulating  center  for  the  pancreas  and  an  inhibitory 
center  for  the  liver.f  When  the  stimulating  center  for  the  pan- 
creas becomes  active,  the  internal  secretion  of  the  pancreas  increases 
and  stimulates  the  inhibitory  center  for  the  liver ;  this  secretion  has 
at  the  same  time  an  inhibitory  influence  on  the  stimulating  center 
for  the  liver  located  in  the  cervical  part  of  the  spinal  cord  above  the 
fourth  cervical  vertebra.  The  production  of  glucose  in  the  liver 
is  thus  diminished  by  a  twofold  influence. 

Chauveau  and  Kaufmann,  besides,  accept  an  inhibitory  influence 

*  "  Comptes  rend.,  "  1 893-1 897. 

f  The  inhibitory  center  for  the  liver  transmits  its  impulses  through  the  "  rami  com- 
municantes  "  of  the  first  four  pairs  of  cervical  nerves.  Its  stimulating  center  transmits 
its  impulses  through  the  "rami  communicantes  "  below  the  first  four  pairs  down  to  the 
sixth  dorsal  vertebra. 


196  DIABETES    MELLITUS    AND    GLYCOSURIA. 

from  the  stimulating  center  for  the  pancreas  on  the  whole  general 
metabolism — the  "histolysis"  in  the  tissues."*  This  histolysis, 
they  further  state,  results  in  the  bringing  to  the  blood  certain  sub- 
stances, which  are  again  carried  to  the  liver  and  there  transformed 
into  glycogen  and  glucose.  The  same  influence  of  the  pancreas 
that  otherwise  inhibits  the  production  of  glucose  in  the  liver  thus 
also  diminishes  its  supply  of  carbohydrates. 

A  section  through  the  spinal  cord  between  the  atlas  and  the 
occipital  bone  separates  the  liver  from  its  inhibitory  centers  and 
delivers  its  stimulating  center  in  the  upper  cervical  cord  from  its 
antagonist ;  at  the  same  time  it  separates  the  pancreas  from  its 
stimulating  center  and  cuts  off  communication  between  the  cere- 
bral centers  and  the  sympathetic  nervous  system  (inferior  cervical 
ganglion),  which  executes  the  impulses  transmitted  from  the  cere- 
bral centers.  The  internal  secretion  of  the  pancreas  does  not  cease, 
but  it  is  considerably  diminished,  and  the  effect  of  the  operation 
is  a  hyperemia,  quite  distinct  from,  and  less  pronounced  than 
that  which  follows  total  extirpation  of  the  pancreas.  Bernard's 
puncture  on  the  floor. of  the  fourth  ventricle  has  the  same  effect,  in 
consequence — according  to  Chauveau  and  Kaufmann — not  of  stim- 
ulation, but  of  a  paralyzing  effect  on  the  nervous  center  of  excitation 
for  the  internal  secretion  of  the  pancreas,  f 

Section  through  the  cord  below  (or  behind)  the  fourth  cervical 
vertebra,  and  between  this  and  the  sixth  thoracic  vertebra,  leaves  the 
communication  between  the  cerebral  stimulating  center  for  the  pan- 
creas and  the  cerebral  inhibitory  center  for  the  liver,  but  cuts  off 
the  stimulating  center  for  the  liver,  and  the  effect  is  not  hypergly- 
cemia, but  distinct  hypoglycemia.  Sections  below  the  sixth  tho- 
racic vertebra  have  no  influence  on  the  amount  of  sugar  of  the 
blood. 

If  the  pancreas  is  extirpated  after  section  of  the  cord  between 


*I  fear  that  it  is  impossible  to  bring  this  part  of  Chauveau's  and  Kaufmann's  theories 
in  accordance  with  the  established  facts  concerning  the  metabolism  of  diabetic  patients. 

I  Kaufmann  later,  after  cutting  all  the  nerves  of  the  liver,  found  that  hyperglycemia 
still  follows  Bernard's  puncture,  and  he  therefore  also  accejHs  a  direct  influence,  outside 
of  the  nervous  system,  of  the  internal  secretion  of  the  pancreas  on  the  liver.  This  inter- 
nal secretion  and  its  inhibitory  influence  on  the  liver  are  diminished  by  the  paralyzing 
influence  of  the  puncture  on  the  stimulating  center  for  the  pancreas. 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 97 

the  fourth  cervical  and  the  sixth  thoracic  vertebra,  diabetes  does  not 
develop,  but  the  hypoglycemia  continues,  the  stimulating  center  for 
the  formation  of  glucose  in  the  liver  being  cut  off.  If,  however,  the 
pancreas  is  first  extirpated,  and  the  same  section  is  made  after  the 
beginning  of  the  diabetes,  hyperglycemia  and  glycosuria  continue. 
Chauveau  and  Kaufmann  explain  this  by  a  certain  autonomy  on  the 
part  of  the  sympathetic  centers  in  the  abdominal  cavity,  which  con- 
tinue to  exercise  stimulating  functions  after  these  have  once  been 
assumed. 

For  the  same  reason  hypoglycemia  continues  if  the  cord  is  first 
severed  between  the  fourth  cervical  and  the  sixth  thoracic  vertebra 
and  section  of  the  medulla  oblongata  above  the  atlas  is  made  after- 
ward. For  the  same  reason  hyperglycemia  continues  after  section 
of  the  medulla  above  the  atlas,  if  later  the  cord  is  severed  between 
the  fourth  cervical  and  the  sixth  thoracic  vertebra. 

After  publication  of  the  foregoing  results  Kaufmann  *  came  to 
the  conclusion,  from  further  experiments,  that  Lepine's  observations 
concerning  diminished  "glycolysis  "  on  the  part  of  the  blood  after 
total  extirpation  of  the  pancreas  are  correct.  Kaufmann,  too,  has 
found  (in  dogs)  diabetic  after  such  extirpation,  a  reduction  of  "gly- 
colysis "  from  I  to  0.77,  or  even  to  0.68,  and  a  normal  or  even 
slightly  decreased  production  of  sugar.  He  maintains  his  pre- 
viously expressed  views,  so  far  as  they  are  not  directly  affected  by 
Lepine's  and  his  own  observations  on  the  effect  of  extirpation  of 
the  pancreas  on  glycolysis.  He  accepts  two  secretions  on  the 
part  of  the  pancreas  :  one,  the  well-known  external  secretion, 
among  whose  functions  is  the  production  of  glucose  from  the  in- 
gested carbohydrates  ;  and  the  other,  the  recently  discovered  inter- 
nal secretion,  among  whose  functions  is  the  production  both  of  a 
glycolytic  ferment  and  of  a  substance  possessing  an  inhibitory  influ- 
ence upon  the  production  of  glucose  in  the  liver.  Kaufmann  thus 
adopts  at  present  the  view  that  will  probably  in  the  future  be  uni- 
versally accepted.  He  believes  that  diabetes  mellitus  may  arise 
from  an  increased  production  of  glucose  in  the  liver  or  from  a  de- 
creased consumption  of  glucose  in  the  tissues,  especially  in  the 
muscles,  or  from  both  of  these  causes  in  combination. 

*  "  Comptes  rend.  hebd.  Soc.  de  Biologic,"  1896. 


I9S  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  results  of  Chauveau's  and  of  Kaufmann's  experiments  tend 
to  make  a  pathologic  unit  of  all  varieties  of  decreased  power  of 
assimilating  carbohydrates.  The  hypothesis  of  the  two  distin- 
guished French  physiologists  must,  however,  be  confirmed  by  a 
vast  amount  of  experimental  work  before  anything  can  be  con- 
sidered settled.  For  the  details  of  Kaufmann's  numerous  and 
laborious  experiments  I  must  refer  to  his  own  works. 

The  clinician  certainly  sees  more  manifestly  the  increased  pro- 
duction than  the  decreased  consumption  of  glucose  in  cases  of 
diabetes.  A  child  of  20  kilograms  bodily  weight  requires  800  calo- 
ries in  twenty-four  hours.  A  diabetic  child  of  equal  weight  may  pro- 
duce one  kilogram  of  glucose,  representing  3692  calories,  in  the  same 
time,  or  so  enormously  much  more  vital  force  than  is  needed  or 
can  be  consumed  that  such  a  production  under  normal  conditions  is 
not  possible. 

As  long  as  we  know  so  little  of  the  laws  governing  the  activity 
of  the  pancreas  and  of  the  liver,  or  are  uncertain  with  regard  to  the 
details  of  the  regulatory  nervous  influence  ;  as  long  as  the  formation 
of  carbohydrates  from,  fats  is  a  mystery  and  the  conditions  for  the 
formation  of  fats  from  carbohydrates  are  unknown  ;  as  long  as  the 
molecular  conditions  necessary  for  the  ultimate  oxidation  are  not 
clearer  than  they  are  at  present,  so  long  shall  we,  even  if  we  accept 
recent  views  on  the  increased  production  of  sugar  and  on  decreased 
"glycolysis"  in  cases  of  diabetes,  be  unable  to  form  any  detailed 
or  clear  opinions  on  the  immediate  cause  or  causes  of  diabetes,  and 
we  shall  do  well  to  abstain  from  too  much  speculation  on  the  sub- 
ject and  to  wait  for  further  conclusions  until  experimental  pathology 
has  provided  us  with  the  necessary  amount  of  established  facts. 

The  normal  human  being  after  ingestion  of  carbohydrates  other 
than  glucose  excretes  no  glucose  in  determinable  quantities  in  the 
urine.  This  fact  was  first  proved  by  Worm-Miiller,  and  I  have  re- 
peatedly verified  the  correctness  of  the  observation  so  far  as  starch, 
cane-sugar,  and  levulose  are  concerned.  After  the  ingestion  of 
enormous  amounts  of  rice  by  healthy  individuals  the  urine  causes 
no  reduction  that  can  be  removed  by  fermentation.  My  own 
experience  has  been  only  with  isolated  instances  in  which  large 
amounts  of  carbohydrate  have  been  taken.  But  healthy  Chinese, 
who  live  almost  exclusively  on  rice,  exhibit  no  glycosuria.     After 


METABOLISM    AND    NUTRITIVE    NEEDS.  1 99 

the  ingestion  of  large  amounts  of  the  different  disaccharids  or 
monosaccharids,  a  comparatively  insignificant  part  of  the  ingested 
saccharid  appears  in  the  urine  in  unchanged  form.  My  own 
numerous  experiments  have  yielded  in  all  essential  respects  the 
same  results  as  Worm-Miiller's.  After  the  ingestion  of  250  grams 
of  cane-sugar,  Worm-Miiller  found  1.8 1  grams  of  cane-sugar  in  the 
urine ;  after  the  ingestion  of  50  grams  of  cane-sugar,  he  found  o.  i 
gram  of  the  same  disaccharid  in  the  urine,  but  not  a  trace  of  glu- 
cose. The  ingestion  of  200  grams  of  lactose  was  followed  by  the 
excretion  of  1.68  grams  of  lactose;  100  grams  of  lactose  by  the 
mouth  yielded  0.32  gram  of  lactose  in  the  urine.  After  the  in- 
gestion of  large  amounts  of  honey,  which  is  a  mixture  of  levulose 
and  glucose,  Worm-Miiller  found  only  glucose  in  the  urine.  Levu- 
lose, however,  obeys  the  same  laws  as  other  saccharids.  After 
the  ingestion  of  150  grams  of  crystallized  levulose  by  a  normal 
individual,  I  found  a  small  quantity  of  reducing  and  fermenting 
substance  in  the  urine  ;  and  by  doubling  the  dose  I  was  able  to  dem- 
onstrate that  the  urine  contained  no  saccharid  other  than  levulose, 
and  to  observe  the  difference  in  levogyration  at  different  tempera- 
tures peculiar  to  this  saccharid. 

Miura  has  lately  observed  that  the  ingestion  of  large  amounts  of 
different  saccharids  by  healthy  individuals  is  followed  by  the  ap- 
pearance in  the  urine  of  small  quantities  of  these  saccharids  exclu- 
sively in  unchanged  form.  Maltose  yielded  maltosuria  ;  levulose, 
levulosuria  ;  lactose,  lactosuria.  Miura  found  also  that  the  ingestion 
of  even  enormous  amounts  of  starch  by  healthy  persons  is  followed 
by  the  appearance  of  no  abnormal  or  unusual  substance  in  the 
urine. 

When  taken  in  large  amounts,  glucose,  like  other  saccharids,  ap- 
pears in  some  degree  unchanged  in  the  urine  in  normal  as  well  as 
in  diabetic  persons.  Normal  individuals,  however,  are  usually  able 
to  assimilate  considerable  amounts  of  glucose  without  exhibiting 
glycosuria.  Worm-Miiller  found,  in  the  urine  of  a  person  whom 
he  accepted  as  normal,  0.47  gram  of  glucose  after  the  ingestion  of 
only  50  grams  of  the  same  monosaccharid.  I  am  inclined  to 
believe  that  in  this  experiment  Worm-Miiller  happened  to  come 
across  a  person  with  the  common,  but  decidedly  pathologic,  weak- 
ening of  the  power  of  assimilation  found  especially  often  in  brain- 


200  DIABETES    MELLITUS    AND    GLYCOSURIA. 

workers  with  some  degree  of  neurasthenia.  A  perfectly  normal 
person  can  usually  take,  on  an  empty  stomach  or  after  a  light 
meal,  at  least  lOO  grams  of  glucose  without  consequent  glycosuria. 
To  again  assure  myself  of  this  fact,  I  had,  shortly  before  this  manu- 
script left  my  hands,  each  of  fifteen  soldiers  in  Stockholm  take  in 
my  presence,  at  lo  A.  m.,  ioo  grams  of  glucose,*  a  few  hours 
after  a  light  breakfast.  Not  one  of  them  afterward  excreted  suffi- 
cient glucose  in  the  urine  to  cause  any  reaction  with  Nylander's  solu- 
tion of  bismuth.  Two  days  afterward  I  gave  200  grams  of  glucose 
in  water  to  each  of  ten  soldiers  ;  neither  after  this  amount  was  there 
in  any  case  sufficient  glucose  in  the  urine  to  yield  a  distinct  reaction 
with  Nylander's  solution  after  four  minutes  of  boiling. 

In  other  instances  200  grams,  and  sometimes,  though  rarely, 
even  100  grams  of  glucose  cause,  in  apparently  healthy  persons, 
some  slight  glycosuria. 

Moritz  mentions  that  large  amounts  of  cane-sugar  cause  in  normal  indi- 
viduals an  excretion  of  cane-sugar  and  of  glucose.  I  maintain  that  when  glucose 
appears  in  the  urine  after  the  ingestion  of  cane-sugar  the  individuals  in  ques- 
tion are  not  normal .f 

De  Jong,  after  some  experiments  with  lactose,  came  to  the  conclusion  that 
large  amounts  cause  in  normal  men  an  excretion  of  lactose  and  of  a  compara- 
tively small  amount  of  fermentable  saccharid.  This  is  contrary  to  the  obser- 
vations of  Worm-Miiller,  Miura,  and  others,  and  I  doubt  that  the  individual  in 
question  was  normal. 

A  large  number  of  observations  have  taught  me  to  conclude  that 
any  person  who  exhibits  glycosuria  after  the  ingestion  of  large 
amounts  of  rice  suffers  from  a  deficient,  distinctly  pathologic  power 

*  Five  of  the  soldiers  received  loo  grams  of  perfectly  pure  glucose  ;  all  the  others 
were  given  "technical"  glucose,  which  contains  some  dextrin.  The  urine  was  secured 
nearly  three  hours  after  the  ingestion  of  the  sugar.  The  excretion  of  the  saccharid  is,  in  the 
large  majority  of  cases,  ended,  or  nearly  ended,  after  that  length  of  time.  The  diuretic 
influence  of  large  amounts  of  glucose  is  often  apparent,  even  when  there  is  no  glycosuria. 

f  I  wish  again  to  call  attention  to  the  fact  that  no  conclusions  can  be  drawn  with 
regard  to  the  details  of  metabolism  in  one  species  of  vertebrates  from  the  results  of 
observations  made  upon  another  species.  Seegen  found  cane-sugar,  glucose,  and 
levulose  in  the  urine  of  dogs  after  the  ingestion  of  large  amounts  of  cane-sugar,  and 
Rubner  found  cane-sugar  and  glucose.  Budge  also  found  glucose  in  the  urine  of  dogs 
after  the  ingestion  of  large  amounts  of  cane-.'-ugar,  but  not  in  man.  As  to  starch,  Hof- 
meister  mentions  that  the  ingestion  of  even  enormous  amounts  causes  no  glycosuria  in 
the  normal  dog. 


METABOLISM    AND    NUTRITIVE    NEEDS.  20I 

of  assimilating  carbohydrates.  To  me,  such  an  individual  is  either 
distinctly  diabetic  or  in  danger  of  becoming  so.  The  appearance  of 
glucose  in  the  urine,  together  with  unchanged  cane-sugar,  after  the 
ingestion  of  large  amounts  of  cane-sugar  is  a  less  serious  manifes- 
tation, but  it  is  not  normal,  and  it  takes  place  in  individuals  who  will 
daily,  under  ordinary  circumstances,  show  some  glycosuria.  The 
smaller  the  proportion  of  glucose  and  the  greater  that  of  cane-sugar 
in  the  urine  under  such  circumstances,  the  more  nearly  is  the  patient 
in  a  normal  condition.  There  are  individuals  who  may  take  from 
200  to  300  grams  of  cane-sugar  without  excreting  determinable 
quantities  of  glucose, — but  only  some  cane-sugar, — and  who  still  do 
not  possess  perfectly  normal  powers  of  assimilation,  but  present 
glycosuria  up  to  0.05  or  o.  i  or  o.  1 5  per  cent,  for  a  short  while  after 
every  dinner  of  mixed  food. 

In  cases  of  diabetes  the  ingestion  of  large  amounts  of  carbohy- 
drate, continued  for  any  considerable  length  of  time,  always  causes 
glycosuria  ;  and  the  more  pronounced  the  glycosuria,  the  more  ad- 
vanced the  glycosuric  dystrophy.  Generally,  no  other  saccharid  is 
then  found  in  the  urine  than  glucose.  This  is  always  the  case  after 
ever  so  large  doses  of  the  polysaccharid  starch.  But  after  very 
large  amounts  of  disaccharids,  or  of  other  monosaccharids  than  glu- 
cose, there  will  appear,  even  in  cases  of  severe  diabetes,  together 
with  a  large  quantity  of  glucose,  a  slight  quantity  of  the  ingested 
monosaccharid  or  disaccharid  unchanged.  This  is  also  the  case  in 
dogs  diabetic  after  extirpation  of  the  pancreas.  Minkowski  found, 
after  administration  of  100  grams  of  levulose,  98.3  grams  of  glucose 
and  2.2  grams  of  levulose  in  the  urine  of  such  a  dog.  Administration 
of  200  grams  of  levulose  yielded  105.6  grams  of  glucose  and  15.6 
grams  of  levulose  in  the  urine. 

The  addition  of  proteids  to  a  certain  portion  of  carbohydrate 
increases  the  glycosuria  in  all  stages  of  the  glycosuric  dystrophy. 
Many  persons  who  are  able  to  take  large  amounts  of  saccharids 
without  the  development  of  glycosuria,  often  excrete  small  quanti- 
ties of  glucose  after  rich  meals  of  mixed  character  ;  and  in  cases  of 
both  light  and  severe  diabetes,  a  portion  of  meat  given  with  a  cer- 
tain amount  of  carbohydrate  increases  the  resultant  glycosuria. 

There  is  only  a  gradual  difference  between  the  different  stages  of 
diabetes  as  to  the  power  of  assimilating  carbohydrates.      All  dia- 
14 


202  DIABETES    MELLITUS    AND    GLYCOSURIA. 

betics  have  this  in  common,  that  they  lose  a  part  of  the  ingested 
and  digested  carbohydrates  during  a  prolonged,  abundant  supply 
thereof;  on  this  single  symptom  is  built  the  whole  dystrophic  group 
of  diabetes  mellitus.  All  cases  and  stages  of  diabetes  also  have  this 
in  common  :  that  they  utilize  a  part  of  the  ingested  and  digested 
carbohydrates.  For  the  slight  deficiency  in  the  power  of  assimila- 
tion that  causes  a  simple  glycosuria,  only  an  insignificant  part  of  the 
ingested  carbohydrates  again  appears  in  the  urine  as  glucose  ;  the 
individual  may  eat  300  grams  of  starch  and  excrete  one  gram  of  glu- 
cose in  the  twenty-four  hours.  In  a  case  of  mild  diabetes  the 
patient  sometimes  may  receive  sixty  grams  of  starch  without  ex- 
hibiting glycosuria,  and  after  long  abstinence  from  carbohydrates  he 
may  even  take  large  amounts  of  cane-sugar  without  manifesting 
any  appreciable  degree  of  glycosuria.  Even  in  the  worst  cases, 
however,  the  physician,  if  he  has  the  courage,  in  spite  of  the  danger 
of  coma,  to  put  his  patient  on  an  exclusively  animal  diet  until  the 
glycosuria  reaches  a  certain  fixed  degree  for  the  twenty -four  hours, 
will  find  that  the  patient,  when  again  allowed  a  certain  quantity  of 
starch,  will  excrete  a  smaller  excess  above  the  former  quantity  of 
glucose  than  corresponds  to  the  digested  part  of  the  ingested  por- 
tion of  starch.  It  seems  that  only  after  extirpation  of  the  pancreas 
in  dogs  the  power  of  assimilating  carbohydrates  may  sometimes  be 
for  a  short  while  completely  destroyed  (Minkowski) ;  but  even  in 
these  cases  a  certain  amount  of  starch  is  usually  assimilated.* 

Almost  all  of  the  glucose  eliminated  from  the  blood  in  cases  of 
diabetes  passes  into  the  urine.  The  saliva,  the  tears,  and  the  sweat 
are  generally  free  from  glucose,  though  it  has  sometimes  been 
found  in  these  in  fractions  of  one  per  cent.f      It  is  sometimes  found 


*  A  dog,  after  extirpation  of  its  pancreas,  received  151  grams  of  starch,  of  which  64.8 
grams  were  found  in  the  feces  and — not  including  small  quantities  possibly  lost  in  the 
intestines  by  fermentation — 86.2  grams  were  digested.  The  urine  contained  99.2 
grams  of  glucose  and  12.22  grams  of  nitrogen.  The  sugar  formed  from  proteids,  com- 
pared to  the  nitrogen  derived  from  them,  bears  a  ratio  as  of  2.8  :  I,  so  that  34.21  grams 
of  glucose  must  have  been  derived  from  proteids  and  64.99  grams  from  the  ingested 
starch.  A  considerable  part  of  the  starch — of  which  54  grams  correspond  to  60  grams 
of  glucose — had  manifestly  been  utilized. 

fToralbi  mentions  a  case  of  "salivary  diabetes"  in  a  hysteric  woman,  without 
glucose,  but  with  a  large  amount  of  oxalates  in  the  urine  and  one  per  cent  of  glucose  in  the 
saliva. 


METABOLISM    AND    NUTRITIVE    NEEDS.  203 

in  serous  fluids;  from  0.14  to  0.27  per  cent,  in  ascites  (Letulle, 
Naunyn),  0.5  per  cent,  in  a  pleuritic  exudate  (Foster),  etc.  Busse- 
nius  found  0.25  per  cent,  in  the  sputa. 

The  greatest  amount  of  glucose  to  the  kilogram  of  bodily  weight 
that  can  be  taken  without  the  development  of  glycosuria  represents 
what  Hofmeister  calls  the  limit  of  assimilation.  This  limit  varies  in 
different  patients,  and  also  varies  in  the  same  patient  at  different  times. 
All  of  those  influences  that  are  known  to  cause  diabetes  or  glyco- 
suria, of  course,  lower  the  limit  of  assimilation.  Excesses  and  emo- 
tions cause  glycosuria  in  normal  individuals  and  increase  it  in  diabet- 
ics. Starvation  or  underfeeding  has  a  bad  influence  in  this  direction  ; 
this  was  discovered  by  Claude  Bernard  and  has  been  elaborately 
studied  by  Hofmeister  (see  Glycosurias).  Muscular  activity  within 
certain  limits  heightens  the  limit  of  assimilation  (Bouchardat,  Zim- 
mer,  Kiilz,  v.  Mering) ;  massage  has  the  same  effect  (Finkler  and 
Brockhaus).  Fatigue,  however,  has  a  contrary  effect,  and  after  long 
marches  or  after  journeys  in  railway  cars  the  diabetic  patient  often 
exhibits  for  several  days  a  lower  power  of  assimilation  than  under 
ordinary  circumstances.  Kiilz  made  an  observation  which  can  be 
easily  verified — viz.,  the  limit  of  assimilation  is  often  higher  early 
than  late  in  the  day.  A  most  important  fact  (see  below)  is  this  : 
that  the  Hmit  of  assimilation  is  higher  after  the  observance  for 
some  time  of  a  strict  diet  and  absence  of  hyperglycemia  and  gly- 
cosuria. Opium,  syzygium  jambulanum,  arsenic,  etc.,  often  increase 
the  limit  of  assimilation ;  in  other  cases  these  drugs  have  no  effect 
whatever.  In  the  course  of  careful  experiments  with  phenacetin, 
which  a  physician  recommended  for  increasing  the  power  of  assimi- 
lation, I  was  able  repeatedly  to  demonstrate  an  increased  glyco- 
suria. Lepine  and  his  disciples  have  lately  given  an  explanation 
of  the  fact  that  the  same  agent  may  have  quite  contrary  effects  in 
different  cases ;  it  increases  both  the  production  and  the  consump- 
tion of  glucose,  so  that  its  effect  on  the  limit  of  assimilation  de- 
pends on  the  relative  state  of  production  and  consumption  in  the 
case.  The  best  remedies,  of  course,  are  those  that  decrease  pro- 
duction and  increase  consumption.  Alcohol  in  small  doses  increases, 
in  large  doses  diminishes,  the  power  of  assimilation.  Fever  decid- 
edly increases  this  power.     Finally,  the  limit  of  assimilation  often 


204  DIABETES    MELLITUS    AND    GLYCOSURIA. 

slowly  sinks,  from  unknown  causes,  in  consequence  of  the  progres- 
sive nature  of  the  glycosuric  dystrophy. 

The  limit  of  assimilation  varies  also  in  the  same  individual  from 
unknown  causes.  Worm-Miiller  gives  a  striking  instance  of  this  : 
V.  C,  previously  mentioned,  received  50  grams  of  glucose  before 
breakfast,  and  excreted  0.47  gram  in  the  urine  during  the  next 
three  hours.  At  another  time,  under  the  same  circumstances,  the 
subject  received  100  grams  without  the  development  of  any  glyco- 
suria whatever.  On  a  third  occasion  glycosuria  appeared  six  hours 
after  the  ingestion  of  100  grams  of  glucose  (rare  !),  and  continued  for 
three  and  one-half  hours,  during  which  time  1.85  grams  of  glucose 
were  excreted. 

Shortly  before  death  and  in  advanced  marantic  states,  the  gly- 
cosuria, ceteris  paribus,  diminishes — not  by  reason  of  an  increased 
power  of  assimilation,  but  on  account  of  impaired  digestion  and  the 
retardation  of  all  the  metabolic  processes.  The  reason  why  glyco- 
suria diminishes  in  cases  of  cirrhosis  of  the  kidneys  remains  to  be 
explained. 

Glycosuria  following  the  ingestion  of  carbohydrates  in  cases  of 
diabetes  (and  after  large  amounts  of  glucose  in  any  person)  begins,  in 
the  enormous  majority  of  cases  at  least,  within  the  first  hour,  and 
generally  a  distinct  reaction  can  be  found  after  half  an  hour.  Bread 
and  well-cooked  rice  seem  to  cause  glycosuria  almost  as  quickly  as 
pure  glucose.  The  larger  part  of  the  glucose  in  the  urine  has  often 
been  excreted  at  the  end  of  the  first  hour  ;  the  curve  afterward 
sinks,  and  after  from  three  to  six  hours  the  urine  in  mild  cases  is 
again  free  from  glucose.  In  cases  of  simple  glycosuria  the  whole 
excretion  may  not  continue  for  more  than  an  hour,  beginning  about 
half  an  hour  and  often  ending  an  hour  and  a  half  after  the  meal. 
Even  with  a  free  diet  the  mild  cases  of  true  diabetes  often  exhibit, 
some  hours  after  a  meal,  no  glycosuria,  and  the  majority  of  such 
patients  present  no  glycosuria  in  the  morning  before  the  first  meal. 
This  is,  therefore,  the  worst  time  for  testing  whether  or  not  an  in- 
dividual is  free  from  diabetes. 

My  patient,  T.,  suffered  from  simple  glycosuria,  and  with  a  perfectly  free 
diet,  including  an  abundant  supply  of  carbohydrates,  excreted  about  2  grams 
of  glucose  in  twenty-four  hours.     Between  9.30  and  10  A.  M.  he  was  free  from 


At  II           " 

95 

At  11.30    " 

145 

At  12       M. 

36 

METABOLISM    AND    NUTRITIVE    NEEDS.  205 

glycosuria,  and  drank   300   grams   of  cane-sugar  in    1000  cu.   cm.  of  water, 
excreting  afterward  as  follows  : 

At  10.30  A.  M.  130  cu.  cm.  of  urine  of  1.030  specific  gravity   and  containing   0.2    per 

cent,  of  sugar. 
"  1.006  "  containing  o.  I  per  cent. 

of  sugar. 
"  1.004  "  containing  about  0.07  per 

cent,  of  sugar. 
"  1. 018  "  containing  0.15  per  cent. 

of  sugar. 
At  12.30  P.  M.     24       "  "  X  "  containing    somewhat 

more  than  o.  i  per  cent,  of 

sugar. 
At    I  "         21        "  "  X  "  containing  less  than  o.  I 

per  cent,  of  sugar. 
At    1.30     "         26       "  "  X  "  containing  traces. 

At    2  "         X         "  "  X  "  containing  faint  trace. 

At    2.30      "        the  urine  did  not  contain  as  much  as  o.oi  per  cent,  of  glucose. 

The  figures  here  given  as  representing  sugar  were  obtained  by  polarization, 
and  thus  refer  to  the  mixture  of  glucose  and  cane-sugar  in  the  urine.  The 
figures  are,  besides,  all  somewhat  too  low,  the  levogyration  of  glycuronic  acids 
not  being  taken  into  account. 

A  medical  student,  X.,  rang  me  up  on  the  telephone,  and  in  a  trembling  voice 
asked  if  he  might  pay  me  a  visit  at  once ;  and  I,  having  had  several  times 
before  a  similar  experience,  at  once  suspected  that  he  had  passed  glucose  in  his 
urine.  The  ingestion  of  250  grams  of  cane-sugar  caused  him  to  vomit  after 
half  an  hour.  The  urine,  however,  passed  a  few  minutes  later  contained  cane- 
sugar  but  no  glucose,  and  reduced  after,  but  not  before,  boiling  with  some 
sulphuric  acid.  On  the  next  day  X.  had  better  luck,  and  was  able  to  retain  200 
grams  of  cane-sugar.  About  two  and  a  quarter  hours  afterward  he  passed  100 
cu.  cm.  of  urine,  with  a  specific  gravity  of  1.022,  and  which,  before  boiling  with 
some  sulphuric  acid,  reduced  as  a  solution  of  glucose  of  0.33  per  cent. ;  but 
after  "inversion  "  (of  the  excreted  cane-sugar)  it  reduced  as  a  solution  of  glu- 
cose of  0.55  per  cent.  In  the  next  sample  of  urine,  passed  three  and  a  half 
hours  after  the  cane-sugar  had  been  taken,  there  was  no  appreciable  amount 
either  of  glucose  or  of  cane-sugar. 

I  consider  X.  more  nearly  a  case  of  true  diabetes  than  he  would  be  if  he  had 
passed  only  cane-sugar  and  no  glucose  ;  but  he  is  better  off  than  he  would  be 
with  greater  glycosuria  and  less  saccharosuria. 

Kiilz  made  it  a  rule  to  give  the  patient  the  allowed  daily  quantity 
of  starch  at  one  meal,  believing  that  it  induced  a  greater  degree  of 
glycosuria  if  given  in  several  portions  at  different  times.  The  re- 
sult, however,  depends  on  circumstances.  If  the  patient's  limit  (or 
power)    of  assimilation  is    small    as    compared  with   the    allowed 


206  DIABETES    MELLITUS   AND    GLYCOSURIA. 

quantity  of  carbohydrates,  this  quantity  given  in  several  doses  may 
occasion  the  presence  of  more  glucose  in  the  urine  than  when  given 
at  one  time  ;  but  if  the  amount  allowed  is  small  as  compared  with 
the  power  of  assimilation,  it  may  induce  less  glycosuria  by  being 
given  in  divided  portions  than  w^hen  given  at  once.  This  is  mani- 
fest both  from  Kialz's  figures  and  from  mere  reasoning  as  soon  as 
the  patient  can  take  any  quantity  of  carbohydrates  without  the  de- 
velopment of  glycosuria. 

Kiilz,  in  addition  to  many  other  services,  also  rendered  that  of 
teaching  us  that  different  kinds  of  carbohydrate  are  assimilated  in 
different  degree  by  diabetics. 

Starch  induces  greater  glycosuria  than  any  other  article  of 
food — greater  even  than  pure  glucose.  The  formula  of  starch  is 
CqH-^^qO-;  that  of  glucose,  CgH^206-  By  taking  up  water,  starch 
will  form  glucose  :  CgHj^O-  -f  H2O  =  CqH^^O^.  The  atomic 
weights  being  for  C  =  12,  H  :=  i,  and  for  O  =  16,  the  foregoing 
equation  yields  12. 6+1.  10+ 16. 5  +  1.2+  16=  12  .  6+  i  .  12  + 
16 .  6,  or  162  +  18  =  180.  In  other  words,  162  grams  of  starch, 
by  taking  up  18  grams  of  water,  will  form  180  grams  of  glucose  ;  or 
9  grams  of  starch  +  i  gram  of  w^ater  will  form  10  grams  of  glucose. 

Cane-sugar  is  a  disaccharid  of  glucose  and  levulose.  Glucose 
causes  marked  glycosuria  in  cases  of  diabetes  ;  levulose,  much  less. 
Thus,  cane-sugar  causes  less  marked  glycosuria  than  starch  or 
glucose. 

Lactose  is  easily  partly  changed  by  fermentation  in  the  bowel 
into  lactic  acid,  w^hich  does  not  give  rise  to  glycosuria,  but  often 
causes  diarrhea,  in  consequence  of  which  more  than  usual  of  the 
ingested  saccharid  passes  off  in  the  feces.  In  so  far,  however,  as 
neither  the  one  nor  the  other  occurs,  lactose  seems  to  give  rise  to 
about  as  marked  a  degree  of  glycosuria  as  does  glucose  itself. 
Kiilz's  patient,  F.  S.,  after  the  ingestion  of  100  grams  of  glucose, 
excreted  8.9  grams  of  glucose  ;  and  after  100  grams  of  lactose,  ex- 
creted 9  grams  of  glucose.*  Fr.  Voit,  in  a  severe  case,  saw  lOO 
grams  of  lactose  increase  the  glycosuria  by  49  grams. 

*  After  five  weeks  of  abstinence  from  carbohydrates  the  power  of  assimilation  had 
increased,  and  loo  grams  of  lactose  gave  rise  to  the  excretion  of  only  4.  i  grams  of  glu- 
cose. The  glycosuria  lasted  about  three  and  one-half  hours,  and  the  larger  part  of  the 
glucose  was  excreted  within  the  first  hour. 


METABOLISM    AND    NUTRITIVE    NEEDS.  20/ 

Galactose  also  gives  rise  to  quite  a  considerable  degree  of  glyco- 
suria. Fr.  Voit  saw  the  glycosuria  increased  by  JO  grams  in  a 
severe  case,  after  the  ingestion  of  lOO  grams  of  galactose. 

Kiilz  has  published  a  report  stating  that  the  polysaccharid  inulin 
and  the  monosaccharid  levulose,  which  are  related  chemically  in 
the  same  way  as  starch  and  glucose,  are  completely  assimilated  by 
diabetics.  As  soon  as  the  price  of  levulose  made  this  substance  of 
practical  value  for  such  a  purpose  I  began  to  use  it  in  cases  of  dia- 
betes ;  in  severe  cases  with  pronounced  autophagia  and  loss  of 
weight  to  lessen  the  daily  nutritive  deficit,  and  in  mild  cases  as  a 
substitute  for  cane-sugar.  I  found  levulose  of  great  value  in  check- 
ing the  loss  of  weight  in  severe  cases,  and  I  believe  it  has  a  power- 
ful effect  in  warding  off  the  coma  for  a  time.  I  constantly  found 
that  levulose  increases  the  glycosuria  in  severe  cases,  and  that  large 
amounts  in  mild  cases  also  cause  glycosuria,*  though  more  of  levu- 
lose than  of  other  saccharids  is  assimilated. 

Inulin,  a  polysaccharid,  is  found  in  unusually  large  quantities  in 
the  tubers  of  Helianthus  tuberosns,  which  is  sometimes  used  for 
food  in  Europe  and  America,  and  is  known  under  the  name  of 
Jerusalem  artichokes  (topinambour).  Boiled  with  diluted  acid  it 
yields  levulose.  It  is  better  assimilated  by  diabetics  than  starch, 
though,  like  levulose,  it  decidedly  increases  the  glycosuria. 

Inosite  does  not  give  rise  to  glycosuria,  even  when  given  in  large 
amounts,  as  in  young  string-beans  (Kiilz).  Inosite  is,  however,  not 
a  saccharid,  and  it  is  not  considered  as  belonging  to  the  carbohy- 
drates.    Maquenne  believes  it  to  be  hexahydroxyl-benzol. 

[As  is  well  known,  inosite  is  found  in  many  parts  of  the  human 
organism,  and  is  often  present  in  the  urine  in  conjunction  with  poly- 
uria, with  diabetes  mellitus  or  insipidus,  and  with  cirrhosis  of  the 
kidney.  Sometimes  glycosuria  is  succeeded  by  inosituria.  In  a 
case  of  diabetes,  Vahl  saw  the  glucose  disappear  and  polyuria 
continue,  and  observed  an  excretion  of  from  eighteen  to  twenty 
grams  of  inosite  in  twenty-four  hours.] 

Mannite,    which  is   a   hexatomic    alcohol,  causes,    according    to 


*  Gruber,  Hale  White,  Haycroft,  Heyse,  Klemperer,  Minkowski,  Palma,  and  others 
have  had  a  similar  experience.  In  the  severe  stage  Palma  found  that  loo  grams  of  levu- 
lose increased  the  glycosuria  by  60.49  grams. 


208  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Kiilz,  no  glycosuria  in  any  stage  of  diabetes,  and  normally  appears 
in  the  urine  in  only  small  quantities.  It  may  be  used  by  diabetics 
as  a  mild  aperient. 

Other  saccharids  than  glucose  are  also  found  in  the  urine,  both 
in  normal  and  in  abnormal  states.  Lactose,  as  has  already  been 
mentioned,  normally  occurs  in  the  urine  of  mothers  during  lactation 
and  in  that  of  sucking  children.  Levulose  has  several  times  been 
found  in  cases  that  have  presented  otherwise  more  or  less  the 
clinical  image  of  diabetes  mellitus,  and  the  same  may  perhaps  be 
true  of  maltose.  Laios,  found  by  Leo  with  glucose  in  a  case  of 
severe  diabetes,  may  possibly  be  a  saccharid,  but  it  is  as  yet  very 
little  known. 

Gorup-Besanez  mentions  levulosuria.  Zimmer  and  Czapek  have  described 
a  case  of  diabetes  with  as  much  as  2.2  per  cent,  of  levulose,  excreted  with 
some  glucose.  Rohmann  and  Wolf  saw  a  case  with  urine  that  turned  the  ray 
of  polarized  light  to  the  right  as  much  as  a  1.6  per  cent,  solution  of  glucose, 
but  reduced  as  a  4.3  per  cent,  solution  of  glucose.  It  contained  in  addition 
to  glucose  a  reducing-substance  that  turned  the  ray  of  polarized  light  to  the 
left,  was  decomposed  by  fermentation,  and  was  thus  in  all  probability  levulose. 
Seegen,  in  1884,  treated  in  Carlsbad  a  case  of  pure  levulosuria.  In  the  follow- 
ing year  Seegen  had  left  the  place  and  the  patient  came  under  my  treatment, 
as  she  did  also  in  1893  and  in  1896.  Both  Seegen  and  Kiilz  have  published 
the  case,  which  clinically  is  more  similar  to  one  of  simple  glycosuria  than  to 
one  of  true  diabetes.  As  it  presents  a  peculiar  interest,  I  briefly  describe  it 
herewith : 

Mrs.  F.,  a  Jewess,  born  in  1837,  knew  of  nothing  else  of  anamnestic  inter- 
est than  that  her  mother  had  suffered  from  obesity  and  probably  from  diabetes, 
the  thirst  being  remarkable  during  the  latter  part  of  life.  The  patient  herself 
was  always  rheumatic,  and  since  childhood  had  from  time  to  time  been  troubled 
by  furuncles.  She  sometimes  suffered  from  dryness  of  the  mouth  and  from 
increased  thirst.  At  no  time,  however,  had  there  been  distinct  polyuria, 
although  there  was  marked  pollakiuria. 

The  patient  was  a  pronounced  neurasthenic  with  a  number  of  the  usual 
symptoms.  She  suffered  from  right-sided  sciatica.  The  knee-jerks  were  some- 
what weakened.  A  sample  of  the  mixed  urine  for  twenty-four  hours  slightly 
reduced  Fehling's  solution.  After  an  abundant  dinner,  with  much  carbohy- 
drate, there  was  a  deviation  to  the  left  of  the  ray  of  polarized  hght  of  0.3°  (with 
Hoppe-Seyler's  instrument),  which  disappeared  for  the  greater  part  after  fer- 
mentation,'when  the  reduction  was  almost  entirely  gone. 

In  1893,  nine  years  afterward,  the  excretion  did  not  amount  to  more  than  0.3 
per  cent,  at  the  utmost,  and  it  was  not  possible  to  decide  with  certainty  whether 
or  not  sonfe  glucose  was  mixed  with  the  levulose. 

In  the  summer  of  1896  the  patient  again  visited  Carlsbad,  being  otherwise 


METABOLISM    AND    NUTRITIVE    NEEDS.  2O9 

in  about  the  same  state  as  eleven  years  before,  i.  e.,  in  fairly  good  health,  suf- 
fering only  from  some  neurasthenic  symptoms  and  from  sciatica  on  one  side. 
The  excretion  of  sugar,  however,  was  larger,  and  in  some  samples  reached 
almost  two  per  cent.  The  urine  contained  no  albumin.  After  removing  the  sac- 
charid  by  fermentation  I  found  only  a  slight  and  uncertain  reducing  effect  on 
the  part  of  the  urine,  but  a  deviation  of  the  ray  of  polarized  light  about  0.15° 
to  the  left.  This  undoubtedly  arose  from  combined  glycuronic  acids,  and 
it  disappeared  after  precipitation  with  ammonia  and  lead  acetate.  This  devia- 
tion taken  into  consideration,  quantitative  determinations  of  the  saccharid,  very 
carefully  performed  by  methods  of  polarization  and  reduction,  perfectly  agreed 
in  results,  and  I  concluded  that  the  urine  contained  no  other  saccharid  than 
levulose.  The  quantity  of  levulose  was  large  enough  to  enable  me  to  observe 
distinctly  the  decrease  in  the  deviation  of  the  ray  of  polarized  light  at  higher 
temperature  peculiar^to  solutions  of  this  substance. 

Seegen,  who  had  the  patient  under  his  care  in  1884,  then  found  3.2  per  cent. 
of  levulose.  Mauthner,  who  analyzed  another  specimen  of  the  urine,  found 
1.59  per  cent,  of  levulose.  The  results  of  polarization  and  reduction  agreed, 
and  the  urine  contained  no  other^  saccharid  than  levulose  in  appreciable 
quantity, 

Kiilz,  in  1886,  wrote  to  the  patient  asking  for  five  liters  of  her  urine,  and 
found  that  the  urine  fermented  slowly  but  completely  on  addition  of  yeast,  form- 
ing alcohol  and  carbonic  acid  ;  that  it  had  a  sweet  taste  on  concentration  ;  and 
that  with  phenylhydrazin  chlorate  and  sodium  acetate  it  yielded  an  osazone 
that  melted  at  205°  C.  (401°  F.),  and  had  the  formula  CgHigOg.  It  yielded 
also  Selivanoff's  reaction  and  turned  the  ray  of  polarized  light  to  the  left. 
This  would  have  assured  an  ordinary  person  of  the  identity  of  the  saccharid 
with  levulose.  Kiilz  found  also  that  levulose  in  "  absolutely  pure,  hard  crys- 
tals "  dissolved  in  water  was  again  precipitated  by  lead  acetate,  and  that  the  sac- 
charid in  the  urine  of  Mrs.  F.  was  precipitated  by  this  salt  only  on  addition  of 
ammonia — a  difference  that,  as  he  himself,  with  all  his  doubts,  remarked, 
might  well  depend  on  the  different  solvent  mediums. 

Le  Nobel  mentions  a  case  of  tnaltosuria  in  a  diabetic  patient  of  sixty-one 
years,  whose  digestion  of  fat  was  much  impaired.  Von  Ackeren  found  maltosuria 
in  a  case  of  carcinoma  of  the  pancreas,  and  Wedenski  possibly  also  saw  such 
a  case.  Further  investigations  seem  necessary,  especially  in  view  of  the  fact 
that  extirpation  of  the  pancreas  causes  in  dogs  only  glycosuria. 

Laios,  found  by  Leo  in  association  with  glucose  in  three  severe  cases  of  dia- 
betes, reduced  (less  than  glucose),  turned  the  ray  of  polarized  light  to  the  left, 
yielded  an  osazone  with  Fischer's  test,  but  did  not  ferment  and  had  no  sweet 
taste. 

If  there  has  been  much  to  say  with  regard  to  the  fate  of  carbo- 
hydrates in  normal  and  diabetic  organisms,  we  may  state  in  com- 
paratively few  words  what  is  necessary  with  regard  to  the  fats, 
however  important  an  item  they  constitute  in  the  dietary  of  a  dia- 
betic patient.  We  know  of  no  direct  changes  in  the  metabolism  of 
fat  in  cases  of  diabetes. 


2IO 


DIABETES    MELLITUS    AND    GLYCOSURIA. 


We  have  seen  that  fat  does  not  increase  the  glycogen  in  the  liver 
or  elsewhere.  We  also  know  that  it  does  not  increase  the  glyco- 
suria in  any  cases  of  diabetes. 

The  absorption  of  fat,  as  has  already  been  mentioned,  is,  in  most 
cases  of  diabetes,  normal.  Fat  is  decomposed,  as  usual,  by  the  bile 
and  the  pancreatic  juice  into  triglycerid,  free  fatty  acids,  and  soaps. 
In  the  chyle  it  is  again  found  almost  exclusively  as  neutral  fat,  and 
is  stored  in  the  liver  and  in  the  muscles.  We  have  seen  that  its  fate 
afterward  is  unknown,  and  that  there  are  various  opinions,  differing 
from  the  one  expressed  by  Nasse,  who  believes  that  it  is  utilized 
and  oxidized  exclusively  in  the  liver,  to  which  the  fat  would  have  to 
return  when  once  stored  anywhere  else. 

Two  qualities  of  fat — its  high  caloric  value  and  that  of  not  in- 
creasing the  hyperglycemia — make  it  an  excellent  food  for  diabetics. 
Unfortunately,  it  is  impossible  to  utilize  practically  to  the  full  ex- 
tent what  might  theoretically  be  expected  from  this  kind  of  food. 
Fat  can  be  tolerated  only  in  quantities  that  are  far  below  the  caloric 
needs  of  the  organism.  Then  fat  does  not  protect  the  proteids  of 
the  organism  as  powerfully  as  carbohydrates  do. 

The  circumstance  that  the  same  number  of  calories  given  in  the 
form  of  carbohydrates  diminish  the  consumption  of  proteids  much 
more  than  an  equal  number  of  calories  in  the  form  of  fat  has  been 
demonstrated  by  Voit,  who  was  able  to  reduce  the  excreted  nitrogen 
with  1 5  per  cent,  by  the  administration  of  carbohydrates,  but  only 
with  9  per  cent,  by  the  administration  of  fat. 

I  insert  the  following  table,  compiled  from  Kaiser's  researches  : 


Daily  Food  in  Grams. 

Calories. 

Nitrogen  in 

Urine 
AND  Feces. 

Gain 

Time. 

Nitrogen. 

Fat. 

Carbo- 
hydrate. 

or 
Loss. 

I.   Four  days,    .    . 
II.   Three  days, 
III.   Three  days,     . 

21. l8 

21.53 

21. lO 

71-65 
217.9 

70.37 

338.2 

0. 
338.2 

2593 

2577 
2581 

20.15 

24.51 
20.17 

+  1.03 
—3.05 
+0.93 

The  most  curious  fact,  that  the  nitrogen  in  the  urine  is  sometimes  increased 
by  the  ingestion  of  fat,  has  several  times  been  observed,  in  contradistinction  to 
the  power  of  conserving  proteid,  which  certainly  belongs  to  some  extent  to  fat. 
Voit  believes  that  this  happens  only  with  a  small  supply  of  proteids  and  a  large 


METABOLISM    AND    NUTRITIVE    NEEDS.  211 

supply  of  fat,  but  Weintraud's  tables  do  not  seem  to  corroborate  this  view. 
Voit  attributes  to  the  fat  two  qualities  with  opposite  results  :  It  has  the  well- 
known  effect  of  conserving  proteids ;  but,  on  the  other  hand,  it  has  a  tendency 
to  increase  the  circulating  proteids.  Weintraud  refers  to  an  analogous 
phenomenon  in  one  of  Nasse's  experiments  ;  A  dog  receives  a  certain  quan- 
tity of  phenol,  excretes  part  of  it  unchanged  and  oxidizes  the  remainder  to 
hydrochinon  ;  with  a  larger  supply  of  fat  the  unchanged  phenol  decreases  and 
the  hydrochinon  increases.  Nasse  considers  that  the  oxidation  of  fat  pro- 
duces free  atoms  of  oxygen.  Still,  we  do  not  know  how  this  is  done,  and  we 
stand  before  a  most  curious  enigma.  I  should  find  it  interesting  to  know  how 
the  diaceturia  and  the  glycosuria  resulting  from  proteids  in  a  severe  case  of 
diabetes  are  influenced  by  a  larger  supply  of  fat,  when  fat  increases  the  nitro- 
gen of  the  urine. 

An  ordinary  civilized  person  can  not  eat  more  than  a  certain 
limited  quantity  of  fat,*  and — worse  luck  for  the  diabetic  patients  ! — 
it  is  not  meat,  but  bread  and  potatoes  (i.  e.,  carbohydrates),  that 
help  him  to  eat  more.  A  comparatively  limited  allowance  of  bread 
— viz.,  from  8o  to  lOO  grams  a  day — markedly  increases  the  capa- 
bility of  eating  a  good  deal  of  fat ;  but  even  then  patients  generally 
can  not  take  more  than  200  or  250  grams  of  this  in  the  twenty-four 
hours  t  without  nausea  and  digestive  disturbances. 

The  formation  of  fat  within  the  organism  in  cases  of  diabetes  is 
impaired  by  the  passing  off  in  the  urine  of  a  part  of  the  carbohy- 
drates of  the  food  which  otherwise  might  form  fat.  In  the  severe 
stage  a  deficit  arises  in  a  like  manner  in  the  formation  of  fat  from 
proteids,  which  may  occur  in  different  ways,  but  which  certainly 
takes  place  in  consequence  of  the  intermediate  formation  of  glyco- 
gen. It  is,  by  the  way,  possible  that  a  better  knowledge  of  the 
details  of  the  formation  of  fat  from   carbohydrates   and  from   pro- 


*  The  Arctic  nationalities  are  capable  of  devouring  large  quantities  of  fat.  In  l868 
I  traveled  through  Lapland  with  no  other  company  than  a  Lap  for  a  servant.  I  was  on 
one  occasion  about  to  throw  away  quite  a  quantity  of  butter  which  began  to  be  rancid. 
The  Lap  protested  against  this  waste,  and,  on  permission,  devoured  the  whole  amount  at 
once  without  the  addition  of  bread  or  of  anything  else. 

f  The  ordinary  articles  of  food  containing  the  largest  percentage  of  fat  are  as  follows  : 

Butter,  with  about  84.4  per  cent,  of  fat  and  from  o.i  to  0.5  per  cent,  of  carbohydrate. 
Olive-oil,           "     99              "              "          "  o.x  "  " 

Lard,  "     76  "  "         "  o.  "  " 

Rich  cheese,     "     30.5  "  "         "  1.5         "  " 

"  Lipanin  "  is  olive-oil  with  about  six  per  cent,  of  free  fatty  acid,  and  is  said  to  taste 
better  and  be  easier  of  digestion  than  neutral  olive  oil. 


212  DIABETES    MELLITUS    AND    GLYCOSURIA. 

teids  in  the  normal  organism  would  contribute  to  a  solution  of  some 
of  the  many  mysteries  of  diabetes.  A  consideration  of  the  forma- 
tion of  fat  within  the  diabetic  organism  leads  me  to  discuss  the  close 
connection  that,  notwithstanding  the  restriction  of  this  formation, 
undoubtedly  exists  between  adiposity  and  diabetes,  and  also  the 
connection  of  both  of  these  dystrophies  with  the  gouty  dystrophy. 
It  would  be  pleasant  and  convenient  to  be  able  to  indicate  the 
nature  of  this  connection  by  saying  that  the  deficient  power  of 
oxidizing  fat  goes  hand  in  hand  with  a  deficient  power  of  oxidizing 
carbohydrates,  and  that  both  these  deficiencies  are  closely  related 
to  the  deficient  power  of  oxidizing  proteids.  But,  with  all  the 
weakness  of  our  present  position,  with  our  exceedingly  imperfect 
knowledge  of  the  pathogenesis  of  each  of  the  three  dystrophies,  we 
now  know  enough  to  understand  how  premature  it  would  be  to 
indicate  in  such  a  manner  the  deep  mystery  of  the  relation  referred 
to.  The  worst  diabetic  can  oxidize  fat  and  other  substances  in 
enormous  quantities.  The  theories  lately  emanating  from  Germany 
in  this  connection  belong,  in  all  their  ingenuity,  in  the  domain  of 
pure  speculation. 

Since  the  end  of  the  i8th  century  physicians  now  and  then  have 
observed  that  the  blood  exhibits  a  grayish  color  in  cases  of  severe 
diabetes,  and  this  color  has  been  found  to  be  due  to  the  presence 
of  an  increased  quantity  of  fat  in  minute  particles.  Diabetic  lipemia 
has  reached  as  high  as  1 1.7  per  cent,  in  man  (Lecanu)  and  12.3  per 
cent,  in  the  dog  (D.  Gerhardt).  It  is  known  that  the  customary 
0.2  or  0.3  per  cent,  of  fat  in  the  blood  may  normally  increase  enor- 
mously after  digestion.  Still,  there  seems  to  be  no  doubt  that  some 
diabetes,  like  tuberculosis  and  alcoholism,  sometimes  causes  the  ap- 
pearance of  a  still  larger  quantity  of  fat  in  the  blood,  a  true  hyper- 
lipemia, and,  sometimes,  though  only  in  rare  cases,  a  consequent 
lipuria.  This  may  be  a  phenomenon  connected  with  the  toxic, 
"protoplasmatic"  disintegration  of  proteids ;  but  at  present  our 
knowledge  of  the  matter  is  restricted  to  what  I  have  already 
mentioned. 

Alcohol  must  not  be  left  out  of  consideration  in  a  discussion  of 
human  food.  It  has  high  caloric  value  ;  a  gram  yields  seven  calories 
gross.     When  large  amounts  are  taken,  about  ninety  per  cent,  of 


METABOLISM    AND    NUTRITIVE    NEEDS.  21 3 

these  calories  are  utilized  (Strassman) ;  when  the  amounts  are  small, 
probably  more  is  utilized  (Hirschfeld).  These  calories  are,  how- 
ever, not  of  high  quality  ;  Miura  has  shown  that  alcohol  protects 
the  proteids  much  less  than  the  same  caloric  amount  of  carbohy- 
drates, and  less  even,  it  seems,  than  the  same  caloric  amount  of  fat. 
In  large  amounts  it  acts  as  a  protoplasmic  poison,  with  a  well-known 
deleterious  influence  in  various  respects,  and  in  such  amounts 
lessens  the  power  of  assimilation  both  in  cases  of  diabetes  and  under 
other  conditions.  In  most  cases  i^  of  a  gram  of  pure  alcohol  per 
kilogram  of  bodily  weight  is  a  fair  allowance  a  day ;  double  this 
amount  is  never  to  be  exceeded  for  habitual  use.  Even  in  these 
amounts  alcohol  ought  always  to  be  taken  miicJi  diluted,  to  avoid 
irritation  of  the  mucous  membranes  and  of  other  structures.  In  this 
condition  and  in  the  doses  stated  it  will  do  no  harm  and  some  good, 
especially  to  diabetics.  It  economizes  fat,  and  if  any  one,  after  taking 
from  twenty  to  thirty  grams  of  alcohol  a  day,  suddenly  observes 
absolute  abstinence,  he  will  always,  ceteris  paribus,  lose  in  bodily 
weight.  In  such  amounts  alcohol  does  not  lessen,  but  rather  in- 
creases, the  power  of  assimilating  carbohydrates  (Kiilz).  If  recent 
investigations  (of  Hirschfeld)  have  not  corroborated  the  claims  for 
alcohol  that  it  facilitates  the  absorption  of  fat,  there  can  be  no  doubt 
about  its  value  in  small  amounts  in  facilitating  the  ingestion  of  larger 
quantities  of  fat  and  in  increasing  the  appetite  in  general.  The 
many  and  terrible  sins  that  mankind  has  committed  with  alcohol 
ought  not  to  make  us  blind  to  its  real  and  most  important  advan- 
tages. There  are  at  present  in  this  country  (Sweden),  as  there  have 
always  been,  a  great  many  drunkards,  who  ruin  themselves  with 
alcohol,  and  a  great  many  cranks  with  an  unwise  and  blind  passion 
for  total  abstinence. 

As  a  faulty  metabolism  of  carbohydrates  distinguishes  the  mild 
stage  of  diabetes  from  a  normal  condition,  so  a  faulty  metabolism  of 
proteids  distinguishes  the  severe  stage  from  both  the  mild  stage  and 
the  normal  condition.  Unfortunately,  a  host  of  questions,  that  can 
not  at  present  be  answered,  present  themselves  with  regard  to  the 
fate  of  proteids  both  in  the  normal  and  in  the  diabetic  organism. 
We  do  not  know  much  more  than  that  proteids  may  form  proteids, 


214  DIABETES    MELLITUS    AND    GLYCOSURIA. 

fat,  and  carbohydrates.*  The  differences  with  regard  to  processes 
both  of  disintegration  and  of  synthesis  between  different  kinds  of 
proteids,  especially  between  the  simpler  proteids  and  those  of  a 
more  complicated  molecular  constitution,  the  proteids  sensii  stric- 
tiori  (nucleins,  mucins),  the  metabolic  differences  between  the 
various  tissues,  the  successive  molecular  steps  on  the  way  to  com- 
plete oxidation,  etc.,  are,  for  the  greater  part,  unknown. 

Our  next  most  important  task  will  be  to  become  better  acquainted 
with  the  conditions  of  production  and  consumption  of  the  three 
substances,  acetone,  diacetic  acid,  and  /S-oxybutyric  acid,  in  cases  of 
diabetes.  We  have  good  general  and  special  reasons  for  consider- 
ing them  to  be  momentarily  present  even  in  healthy  organisms, 
though  the  ;9-oxybutyric  acid,  the  mother-substance  of  the  others, 
is  normally  quickly  converted  into  diacetic  acid,  this  acid  into 
acetone,  and  acetone  into  carbonic  acid  and  water.  I  shall  return 
to  this  subject  later. 

The  difference  in  the  metabolism  of  the  proteids  between  the  mild 
and  the  severe  stage  of  diabetes  begins  in  the  liver.  I  have  stated 
that  if  in  the  mild  stage  the  carbohydrates  are  restricted  below  the 
patient's  limit  of  assimilation,  the  formation  of  glycogen  in  the 
liver  in  great  probability  takes  place  just  as  it  does  in  a  normal  indi- 
vidual upon  the  same  diet.  In  cases  of  severe  diabetes,  however, 
the  formation  of  glycogen  is  restricted  under  all  dietetic  conditions, 
and  even  a  part  of  the  products  of  proteids  passes  off  in  the  urine 
as  glucose. 

The  details  of  the  formation  of  carbohydrates  from  proteids  are 
not  known.  We  do  not  know  if  all  the  glucose  derived  from  pro- 
teids must  first  become  glycogen,  but  we  have  good  reason  for 
believing   that  there    is    no  such  necessity  and  that  proteids   can 

*  The  formation  of  proteids  from  peptones  and  albuminoids  need  not  detain  us,  and  we 
have  already  spoken  of  the  formation  of  carbohydrates  from  proteids.  There  is  still  some 
slight  doubt  whether  proteids  can  or  can  not  form  fat  directly  and  without  first  forming 
glycogen,  notwithstanding  the  cellular  manifestations  in  regressive  metamorphosis  or  after 
certain  poisons,  the  formation  of  the  acid  of  palmitin  (Salkowski)  and  other  productions 
after  death  (Salkowski,  Lehmann),  the  supposed  formation  of  fat  from  proteids  in  larvse 
(Hofmann),  the  abundant  formation  of  milk  even  with  an  exclusive  diet  of  meat  in 
bitches  (Subbotin,  Voit,  Kemmerich),  and  the  disappearance  in  the  organism  of  carbon 
with  a  similar  diet  (Pettenkofer  and  Voit,  E.  Voit). 


METABOLISM    AND    NUTRITIVE    NEEDS.  21 5 

directly  form  other  carbohydrates  than  glycogen.  Hammarsten 
isolated  (from  the  pancreas,  the  liver,  and  the  mammary  gland)  a 
nucleo-proteid  which,  when  boiled  with  a  diluted  mineral,  yielded 
a  reducing  substance  that  was  proved  to  be  a  pentose.  Hammar- 
sten admits  the  separation  of  a  molecule  of  carbohydrate  from  the 
proteids  of  a  more  complicated  structure  (nucleins,  mucins).  Pavy 
considers  the  proteids  glucosids  that,  boiled  with  diluted  acids, 
yield  saccharids  and  proteids  of  less  complicated  structure,  and  has 
produced  carbohydrates  from  the  albumen  of  eggs  and  from  fibrin. 
Kravkow's  researches  have  led  to  similar  conclusions  with  regard  to 
some  kinds  of  proteids.  Kassel  produced  formic  acid  and  levulinic 
acid  by  the  action  of  sulphuric  acid  on  nuclein.  Levulinic  acid  has 
always  shown  itself  as  a  derivative  of  carbohydrates. 

It  is  the  presence  of  derivatives  of  proteids  in  the  urine  that  dis- 
tinguishes severe  from  mild  diabetes.  The  glucose  in  severe  cases 
is  partly  derived  from  proteids  ;  the  acetone,  the  diacetic  acid,  and 
the  /?-oxybutyric  acid  in  such  cases  are  believed  to  be  derived 
exclusively  from  proteids. 

If  in  a  case  in  the  mild  stage  the  carbohydrates  of  the  food  are 
restricted  below  the  patient's  limit  of  assimilation  his  urine,  as  is 
well  known,  remains  free  from  glucose  and  does  not,  so  far  as  we 
know  at  present,  differ  from  the  urine  of  a  normal  person  livittg  on 
the  same  diet. 

For  practical  reasons  I  here  deviate  from  the  straight  line  of  ex- 
position to  show  the  truth  of  this  last  assertion. 

Among  certain  derivatives  of  proteids  in  the  urine  in  the  mild 
stage  we  are  chiefly  interested  in  urea,  uric  acid,  and  acetone  (the 
diacetic  and  /5-oxybutyric  acids  belong  exclusively  to  the  severe 
stage). 

Acetone  was  first  discovered  in  a  case  of  severe  diabetes.  It  is 
undoubtedly  increased  in  such  cases.  Engel  found  2.8  grams, 
which  is  a  rare  figure.  In  normal  individuals  the  daily  excretion  is 
only  about  0.0 1  gram  (v.  Jaksch) ;  but  it  is  often  increased  in 
children,  whose  breath,  by  the  way,  sometimes  under  apparently 
normal  conditions  smells  of  acetone.  It  is  increased  also  with 
lactosuria  during  lactation,  being  probably  derived  from  casein 
(Guckelberg,  V.  Jaksch),  and  after  the  ingestion  of  certain  poisons, 
during  starvation,  in  febrile  states,  in  eclampsia  and  epilepsy,  lyssa. 


2l6  DIABETES    MELLITUS    AND    GLYCOSURIA. 

cachexia,  disturbances  of  digestion,  and  mental  diseases.  It  is 
normally  increased  when  carbohydrates  are  excluded  from  the  diet 
and  with  a  purely  animal  diet.  Von  Jaksch  states  that  in  some  mild 
cases  of  diabetes  it  does  not  occur  in  larger  quantities  than  in  nor- 
mal individuals  using  the  same  food,  and  Hirschberg's  researches 
point  to  a  similar  result.  At  present  it  is  not  proved  that  there  is 
any  increase  of  acetone  at  all  in  the  mild  stage  of  diabetes,  and, 
even  in  that  event,  it  is  not  known  under  what  circumstances  or  in 
what  class  of  cases  (see  below). 

As  to  urea,  it  is  now  known  that  in  the  large  majority  of  cases 
of  diabetes  it  is  not  present  in  the  urine  in  larger  quantities  than  in 
normal  individuals  under  the  same  dietetic  conditions.  Only  in  the 
very  severe  cases  with  the  toxic  or  protoplasmic  disintegration  of 
tissues  is  the  patient  supposed  to  excrete  more  urea  than  a  normal 
person  upon  the  same  food. 

The  quantity  of  uric  acid,  about  which  only  the  newest  analytic 
methods  give  reliable  information,  varies  greatly  in  normal  indi- 
viduals. Naunyn  and  Riess,  by  a  method  of  their  own,  found  from 
0.16  to  1.05  grams  ;  Kiilz,  by  the  same  method,  from  0.06  to  0.76 
gram  ;  Bouchardat,  more  than  three  grams ;  Hartz,  in  six  cases  of 
diabetes,  found  at  the  utmost  between  1.5  and  2  grams  of  uric  acid 
in  the  urine  in  twenty-four  hours.  Neither  from  these,  nor  from 
Bischofswerder's,  nor  any  other  researches  can  it  be  concluded  that 
a  greater  or  lessei"  excretion  of  uric  acid  takes  place  in  diabetics  than 
in  normal  individuals.  To  gain  some  notion  of  the  difference  between 
normal  individuals  and  diabetics  in  this  respect,  it  would  be  necessary 
to  compare  a  large  number  from  each  of  the  two  classes  under  the 
same  dietetic  conditions,  and  especially  with  the  same  quantity  of  in- 
gested nucleins.  On  account  of  the  absence  or  presence  of  sediment, 
and  on  no  better  basis  than  "  uroscopy,"  it  has  been  said  that  uric 
acid  is  diminished  in  the  severe  stage  and  increased  in  the  mild  stage 
of  diabetes.  Some  writers  have  also  (since  1855)  spoken  of  a  ''dia- 
betes alternans,''  with  alternation  in  the  excretion  of  large  quantities 
of  uric  acid  and  of  glucose  (Claude  Bernard,  Bouchardat,  Brogniart, 
Budde,  Coignard,  Charcot,  Ebstein).  I  am  far  from  certain  that 
such  an  alternation  takes  place,  and  I  am  pretty  certain  that  its 
existence  has  never  been  proved.  As  is  well  known,  the  sediment 
is  by  no  means  an  adequate  expression  of  the  quantity  of  uric  acid 


METABOLISM    AND    NUTRITIVE    NEEDS.  21/ 

present.  A  urine  containing  a  greater  amount  of  uric  acid  may- 
keep  the  whole  amount  in  solution,  while  another  urine  containing 
less  uric  acid  may  present  a  part  of  it  in  the  form  of  a  sediment. 
In  mild  gouty  cases  of  diabetes  the  urine  often  contains  consider- 
able sediment.  All  that  can  at  present  be  safely  asserted  is  that  a 
marked  sediment  of  uric  acid  indicates  a  mild  case  of  diabetes,  and 
that  such  a  sediment  is  absent  from  the  pale  greenish-yellow  urine 
of  severe  cases. 

Kreatin  was  found  by  Winogradofif  in  small  quantities  and  by  Sena- 
tor in  large  quantities  in  diabetic  urine  (up  to  two  grams  a  day). 
From  their  researches,  and  from  those  of  Bunge  and  St.  Johnson, 
we  infer  that  kreatin  and  kreatinin  are  in  most  cases  of  diabetes 
(and  apart  from  toxic  disintegration  of  tissue),  under  the  same  diet- 
etic conditions,  to  be  found  in  the  urine  in  the  same  quantity  as  in 
normal  urine. 

In  mild  cases  the  amount  of  ammonia  does  not  exceed  that  which 
may  be  found  normally  with  an  abundant  supply  of  proteids.  Only 
in  severe  cases  with  "  acidosis "  does  it  attain  large  proportions, 
and  it  may  equal  as  much  as  twelve  grams  in  twenty-four  hours — 
solely  because  the  acids  have  a  greater  affinity  for  it  than  they  have 
for  urea. 

Boedeker  found  in  diabetic  urine  a  substance  that  he  called 
alkapton,  but  which  is  found  also  in  the  urine  of  normal  children 
and  of  other  nondiabetic  persons.  In  some  instances  the  sub- 
stance found  may  possibly  have  been  pyrocatechin.  It  is  also 
represented  by  uroleucin  and  glycosuric  acid,  and  is  otherwise 
known  as  homogentisinic  acid.  It  can  not  be  said  to  bear  any 
special  relation  to  diabetes  ;  according  to  Baumann  and  Walkow,  it 
is  formed  in  the  bowel  under  the  influence  of  certain  micro- 
organisms. 

Hippuric  acid  has  been  found  in  diabetic  urine  (from  o.  i  to  i 
gram)  by  Lehmann ;  it  is  found  also  in  normal  urine,  and  is  in- 
creased in  febrile  states,  in  diseases  of  the  liver,  and  in  neuroses.  It 
arises  in  the  course  of  the  putrefaction  of  proteids,  and  may  be  found 
equally  apart  from  as  with  diabetes,  whenever  putrefactive  processes 
are  taking  place. 

The  low  fatty  acids  (formic,  acetic,  butyric,  propionic)  are  but 
rarely  found  in  diabetic  urine  recently  passed  (v.  Jaksch) ;  they  are 
15 


2l8  DIABETES    MELLITUS    AND    GLYCOSURIA. 

sometimes  found  in  normal  urine  and,  according  to  Rumpf,  they  are 
present  in  normal  quantities  in  mild,  but  in  increased  quantities  (up 
to  ten  grams)  in  severe  cases.  Purely  diabetic  lipaciduria  is  a 
feature  exclusively  of  such  cases. 

Lipuria  is  sometimes  found  in  normal  persons  after  the  ingestion 
of  large  amounts  of  fat,  and  is  found  in  association  with  the  most 
widely  different  pathologic  conditions,  chiefly  after  the  taking  of 
certain  poisons  and  in  cachectic  or  marantic  states.  Purely  dia- 
betic lipuria,  like  purely  diabetic  lipaciduria,  is  a  feature  of  severe 
cases. 

Lactic  acid  in  its  two  slightly  different  modifications  may  occur  in 
the  urine  in  cases  of  diabetes.  Minkowski  in  a  severe  case  found  the 
levogyrate  acid  in  the  blood  ;  Rumpf  in  a  similar  case  found  it  in 
the  urine.  We  have  already  seen  that  lactaciduria  is  a  common 
phenomenon  in  conjunction  with  glycosuria  after  some  poisons;  it 
has  also  been  found  in  cases  of  acute  yellow  atrophy  of  the  liver. 
Colasanti  and  Moscatelli  found  lactic  acid  in  small  quantities  in  the 
urine  of  soldiers  after  forced  marches.  We  are  at  present  too  little 
acquainted  with  the  conditions  for  the  appearance  of  lactic  acid  in 
the  urine  to  decide  its  relation  to  diabetes.  Still,  it  seems  certain 
that  it  may  appear  under  other  conditions. 

We  undoubtedly  find  in  cases  of  diabetes — especially,  as  it  seems 
to  me,  in  mild  cases — an  increased  amount  of  oxalic  acid  in  the 
urine.  I  have  sometimes  seen  quite  an  enormous  number  of  the 
small  crystals  of  calcium  oxalate  in  cases  of  simple  glycosuria,  when 
an  abundant  supply  of  carbohydrates  has  given  rise  to  only  a  trace 
of  glucose  in  the  mixed  urine.  I  am  much  more  inclined  to  accept 
(with  Prout)  an  alternation  between  oxaluria  and  glycosuria  in  cer- 
tain cases  than  an  alternating  excretion  of  glucose  and  uric  acid. 
Fiirbringer  saw  oxaluria  and  oxaloptysis  in  a  diabetic  patient. 
There  are  many  records  of  oxaluria  in  cases  of  diabetes,  and  it  may 
exist  without  being  discovered  by  the  microscope,  the  calcium 
oxalate  being  kept  in  solution  by  the  acid  phosphates,  which  are 
often  present  in  large  quantities  in  the  urine  of  diabetic  patients  eating 
much  meat.  Apart  from  alimentary  and  normal  oxaluria  and  the 
"symptomatic"  oxaluria  associated  with  some  other  diseases  and 
pathologic  states,  and  apart  from  diabetic  oxaluria,  there  is  a  form 
known  as  (Cantani's)  idiopathic  oxaluria  with  its  neurasthenic  and 


METABOLISM    AND    NUTRITIVE    NEEDS.  2ig 

slight  dystrophic  symptoms.  This  idiopathic  glycosuria  is  probably 
identical  with  the  oxaluria  found  in  neurasthenic  individuals  with  or 
without  glycosuria.  On  the  other  hand,  and  so  far  as  is  known  at 
present,  there  are  many  cases  of  glycosuria  or  diabetes  without 
oxaluria. 

The  abundant  ingestion  of  proteids  in  cases  of  diabetes,  often 
associated  with  habitual  constipation  and  protracted  retention  of  the 
feces  in  the  bowels,  causes  an  increase  in  the  products  of  putrefac- 
tion. We  thus  find  sulphuric  acid  combined  with  aromatic  alco- 
hols (phenol,  indoxyl,  etc.)  and  the  combined  glycuronic  acids  in- 
creased. The  sulphuric  acid  in  the  sulphates  is  also  increased  by 
the  customary  abundant  amount  of  animal  food  ;  but  we  have  no 
reason  to  believe  that  in  mild  cases  of  diabetes,  and  apart  from  toxic 
disintegration,  the  whole  amount  is  more  greatly  increased  than  it 
would  be  under  similar  circumstances  in  nondiabetic  individuals. 
The  total  acidity,  too,  is  often  increased  in  cases  of  diabetes,  as 
Derignac  and  others  have  noted,  but^  in  mild  cases  only  from  the 
causes  just  mentioned.  In  severe  cases  the  diacetic  and  /3-oxybu- 
tyric  and  other  acids  contribute  to  the  increase  of  the  total  acidity. 

Phosphaturia  will  be  considered  later. 

Inosite  is  found  in  cases  of  diabetes,  but  also  in  all  states 
attended  with  polyuria.  Reichardt's  dextrin  was  found  in  the  urine 
in  a  case  of  mild  diabetes,  but  it  is  not  known  whether  or  not  it  has 
any  connection  with  diabetes.  The  same  is  true  with  regard  to 
Leube's  glycogen,  which  may  perhaps  be  identical  with  Reichardt's 
dextrin.  Lemaire's  isomaltose  is  not  well  known,  and  Wedenski 
found  in  normal  urine  something  that  may  be  maltose.  Gum  or 
achrooglycogen  is  also  found  in  normal  urine  (Landwehr,  Weden- 
ski, Amann). 

Kiilz  and  T.  Vogel  found  pentoses  (from  0.25  to  0.43  gram  a 
day)  in  cases  of  severe  diabetes.  The  test  for  phenylhydrazin  in 
normal  urine  also  yields  some  crystals  of  osazone,  which  melt  at 
165°  C.  (329°  F.),  and  which  probably  are  pentoses  (E.  Holmgren). 

Leon  Kalm  found  urobilin  absent  in  two  severe  cases  of  diabetes. 
Vogel  and  Neubauer  mention  this  absence  in  normal  urine. 

M.  Ch.  Ulrich  has  come  to  the  conclusion  that  leucin  and  tyrosin 
are  present  in  normal  urine,  but  absent  in  cases  of  severe  diabetes. 
(The  crystals  seen  by  Roque,  Devie,  and  Hugonenq  in  the  Hver, 


220  DIABETES    MELLITUS    AND    GLYCOSURIA. 

then,  could  not  have  been  leucin  and  ty rosin.)  Whether  the  two 
substances  are  present  in  or  absent  from  the  urine  in  mild  cases  of 
diabetes  is  not  known. 

In  severe  cases  of  diabetes  the  diastatic  and  the  peptic  ferment 
have  been  found  to  be  increased  in  the  urine  (Hoffmann,  Stadel- 
mann,  Leo,  and  others).  Lepine  found  no  increase  of  the  diastatic 
ferment,  and  nothing  is  known  of  such  an  increase  in  mild  cases. 

Albic  found  diabetic  urine  strongly  toxic  (from  ptomains,  di- 
amins,  etc.).  Neubauer  and  Vogel  mention  that  diabetic  urine  apart 
from  cachexia  is  not  more  toxic  than  other  urine,  which  indicates 
that  the  increase  of  toxic  substances  is  a  feature  of  severe  cases  ex- 
clusively. 

From  the  foregoing  brief  exposition  it  may  be  concluded  that  we 
do  not  at  present  know  of  any  pathologic  substance  that  is  invariably 
present  in  the  urine  in  mild  cases  of  diabetes.* 

Traube's  definition  of  severe  diabetes  is  the  best  even  to-day  :  A 
state  that  is  attended  with  excretion  of  glucose  in  the  urine,  even  when 
carbohydrates  are  excluded  from  the  food,  and  when  a  pure  diet  of 
proteids  (and  of  fat)  is  observed.  It  will  be  understood  that  this 
does  not  mean  that  severe  diabetes  is,  while  light  diabetes  is  not, 
attended  with  the  production  of  carbohydrates  from  proteids  ;  it 
having  been  proved  long  ago  that  proteids  give  rise  to  glycogen 
and  thus  indirectly  (and  perhaps  also  directly)  to  glucose,  in  all 
organisms,  diabetic  in  any  stage,,  or  nondiabetic.  In  the  mild 
stage,  however,  the  patient,  while  losing  (some  of)  the  glucose 
derived  from  carbohydrates,  has  the  power  of  assimilating  at  least 
all  of  the  glucose  derived  from  proteids.  In  the  severe  stage, 
though  the  patient  always  retains  the  capability  of  utilizing  a  part 
of  the  glucose  derived  from  carbohydrates,  he  has  lost  the  power 
of  utilizing  all  of  the  glucose  derived  from  proteids. 

On  this  point,  again,  we  find  that  mild  and  severe  diabetes  are 
only  stages  of  the  same  dystrophy,  and  that  there  are  intermediate 
states  representing  the  gradual  transition  from  the  one  to  the  other. 
There  are  patients  who,  when  carbohydrates  are  excluded  from  the 
food,  present  no  glycosuria  with  a  certain  daily  supply  of  proteids, 


'*  The  substances  whose  connection  with  mild  diabetes  it  seems  most  interesting  to 
investigate  are  acetone,  oxalic,  glycuronic,  and  lactic  acids. 


METABOLISM    AND    NUTRITIVE    NEEDS.  221 

but  who  again  excrete  glucose  if  the  amount  of  proteids  is  in- 
creased, though  carbohydrates  are  still  excluded  (Naunyn,  Licht- 
heim,  Troye,  Weintraud). 

I  wish,  however,  to  insist  most  forcibly  that  the  hyperglycemia 
and  the  glycosuria  resulting  from  proteids  do  not  constitute  the 
most  important  metabolic  difference  between  the  mild  and  the 
severe  stage  of  diabetes.  The  main  and  all-important  difference 
between  mild  and  severe  diabetes  is  the  production  in  the  latter 
of  certain  acid  toxins  in  the  blood  and  in  the  urine. 

This  brings  us  again  to  a  consideration  of  that  most  interesting 
trio  already  touched  upon :  acetone,  diacetic  acid,  and  /3-oxybutyric 
acid.*  The  latter  two  substances,  and  especially  the  last,  are  im- 
portant factors  in  the  acid  diathesis,  the  "acidosis,"  existing  in 
cases  of  severe,  but  not  of  mild,  diabetes. 

All  three  substances,  free  from  nitrogen  as  they  are,  originate  in 
proteids,  and  seem  to  appear  as  soon  as  the  organism,  from  some 
cause  or  other,  attacks  its  own  proteid  tissues  ;  they  all  three  appear 
during  starvation,  and  in  the  course  of  different  states  producing 
inanition. 

Though  there  is  little  doubt  as  to  the  intimate  connection  of  the 
three  substances  as  representing  different  stations  on  the  way  to 
complete  oxidation  of  molecules  derived  from  proteids,  the  reason 
why  the  course  of  oxidation  is  interrupted  in  cases  of  severe  diabetes 
and  in  some  other  states  will  probably  continue  for  a  long  while  to 
be  a  puzzle  to  every  student  of  diabetes.  There  are  good  reasons 
for  believing  that  the  same  disintegrated  proteids  as  alone  give  rise 
to  glucose  in  the  urine  in  cases  of  severe  diabetes  also  give  rise 
to  /3-oxybutyric  acid  and  its  derivatives,  diacetic  acid  and  acetone. 
The  curves  representing  the  glucose  derived  from  proteids  and 
the  ^-oxybutyric  acid  show  unmistakable  parallelism  (Naunyn). 
Any  one  that  follows  a  case  of  diabetes  in  its  development  through 
the  mild  into  the  severe  stage  will  gain  the  positive  impression  of  a 


*  Acetone  [CgHgO]  is  a  watery,  strong-smelling,  neutral  liquid,  boiling  at  56.5°  C. 
(133-7°  F.). 

Diacetic  acid  [C^HgOg]  is  a  thick,  colorless,  hygroscopic  liquid,  which  is  decomposed 
into  carbonic  acid  and  water  at  a  temperature  below  100°  C.  (212°  F.). 

/?-oxybutyric  acid  is  a  colorless  liquid  of  the  consistency  of  syrup,  which  by  oxidation 
easily  yields  acetone.     Boiled  with  acid  water,  it  yields  a-crotonic  acid  and  water. 


22  2  DIABETES    MELLITUS    AND    GLYCOSURIA. 

parallelism  between  the  glycosuria  due  to  proteids  on  the  one  hand, 
and  the  three  substances  named  on  the  other.  The  patient  in  the 
distinctly  mild  stage  can  usually  take  some  carbohydrate  without 
the  development  of  glycosuria.  During  this  state  there  is  no 
/9-oxybut}^ric  acid  and  no  diacetic  acid  in  the  urine  so  long  as  the 
patient  utilizes  a  sufficient  amount  of  calories  in  his  food,  and  there 
is  under  these  conditions  no  more  acetone  than  in  the  urine  of  a 
normal  person  using  the  same  kind  of  food  (see  below).  As  the 
dystrophy  advances,  the  amount  of  acetone  in  the  urine  probably 
increases  before  either  of  the  acids  has  made  its  appearance. 
There  is  at  present  some  uncertainty  as  to  the  exact  place  in  the 
development  of  the  glycosuric  dystrophy  where  this  happens  (see 
below).  So  long  as  the  patient,  with  exclusion  of  carbohydrates 
from  the  food,  becomes  free  from  glycosuria,  he  presents  no  diacet- 
uria  with  a  sufficient  supply  of  calories.  After  some  time,  how- 
ever, in  slowly  developing  cases, — generally  some  years  after  the 
beginning  of  the  diabetes, — the  patient,  even  during  a  period  of  ex- 
clusion from  the  food  of  carbohydrates,  exhibits  a  distinct,  though 
slight,  glycosuria.  At  this  stage  the  physician  finds  for  the  first  time 
Gerhardt's  reaction  in  the  urine  with  ferric  chlorid,  though  he  has 
taken  care  to  provide  his  patient  with  an  adequate  supply  of  calo- 
ries. There  is  now  also  an  increased  amount  of  acetone  in  the  urine, 
and  there  is  a  faint  odor  of  this  substance  on  the  patient's  breath. 
The  urine  contains  no  y5-oxybutyric  acid.  The  patient  is  likely  to 
lose  flesh,  but  he  is  only  in  the  first  part  of  the  severe  stage,  and 
he  is  often  able  to  maintain  his  weight.  There  is  a  possibility  that 
this  can  be  effected  only  by  some  increase  in  the  amount  of  fat 
covering  a  loss  of  proteid.  As  the  dystrophy  advances  the  glyco- 
suria due  to  proteids  increases,  and  pari  passii  Gerhardt's  reaction 
deepens  in  intensity  until  it  gives  rise  to  a  dark  bluish-red  color, 
the  breath  smells  more  and  more  strongly  of  acetone,  and  autoph- 
agy  becomes  more  and  more  manifest.  Long  before  these  last 
symptoms  become  extreme,  but,  in  slowly  developing  cases,  often  a 
considerable  time  after  the  transition  from  the  mild  to  the  severe 
stage,  the  physician,  after  having  removed  the  glucose  from  the 
urine  by  fermentation,  and  after  having  removed  other  levogyrate 
substances  than  /S-oxybutyric  acid  (combined  glycuronic  acids)  by 
precipitation  with  ammonia  and  lead  acetate,  still  finds  a  distinct 


METABOLISM    AND    NUTRITIVE    NEEDS.  223 

levogyration  in  the  polarimeter.  He  can  afterward  observe  how 
the  /5-oxybutyric  acid  increases  in  quantity  as  the  case  advances 
in  the  severe  stage. 

It  has  generally  been  accepted  that  when  /3-oxybutyric  acid,  the 
mother-substance  of  diacetic  acid  and  acetone,*  appears  in  the  urine, 
these  latter  substances  are  certain  also  to  be  present.  It  has  also 
been  quite  generally  accepted  that  /S-oxybutyric  acid  is  present 
only  in  urine  that  yields  a  marked  Gerhardt's  reaction,  or,  in  other 
words,  in  urine  that  contains  a  considerable  amount  of  diacetic  acid. 
In  general,  the  rule  holds  good  that  when  one  finds  the  /3-oxybu- 
tyric acid, — which  undoubtedly  denotes  a  more  advanced  period  in 
the  severe  stage  and  a  greater  autophagy  than  either  of  the  two  other 
substances, — these  are  also  to  be  found.  It  also  seems  certain  that 
when  diacetic  acid  is  found,  which  is  not  rarely  the  case  when  no 
/3-oxybutyric  acid  is  present,  acetone  is  usually  found  in  an  abnor- 
mally increased  quantity.  The  appearance  of  the  latter  substance 
is  a  less  grave  phenomenon  than  that  of  diacetic  acid,  and  this,  again, 
is  less  grave  than  that  of  /3-oxybutyric  acid.  It  seems  certain, 
however,  that  the  quantitative  relations  of  the  three  substances  are 
not  fixed,  and  that  one  can  not,  from  the  quantity  of  one,  reach  a 
conclusion  as  to  the  quantity  of  either  of  the  others.  It  is 
especially  worth  remembering  that  the  common  idea  with  regard  to 
a  necessarily  pronounced  Gerhardt's  reaction  in  all  urine  containing 
/3-oxybutyric  acid  is  a  false  one.  I  have  several  times  found  an 
unmistakable  amount  of  /3-oxybutyric  acid  in  urine  that  has  not 
yielded  with  the  solution  of  ferric  chlorid  the  dark  bluish-red 
color  of  considerable  quantities  of  diacetic  acid,  but  only  a  light, 
transparent  red.  Naunyn  and  Albertoni  have  made  analogous 
observations.  I  find  in  Neubauer  and  Vogel's  last  edition  a  note 
(after  Stadelmann  ?)  that  /3-oxybutyric  acid  may  be  present  without 
any  diacetic  acid  at  all.     This  certainly  is  not  a  common  occurrence. 

Gerhardt's  reaction,  if  pronounced,  indicates  constant  danger 
of  coma.  If  the  reaction  is  absent  or  only  faint,  this  seems  to 
indicate  the  absence  of  any  considerable  quantity  of  /3-oxybutyric 


*  Minkowski  demonstrated  the  relation  of  /?-oxybutyric  acid  as  the  mother-substance  of 
diacetic  acid  and  acetone.  By  administering  /3-oxybutyric  acid  to  diabetic  dogs  he  caused 
the  appearance  or  the  increase  of  both  of  the  other  substances  in  the  urine. 


224  DIABETES    MELLITUS    AND    GLYCOSURIA. 

acid,  and,  unless  the  general  state  is  extremely  bad,  there  is  then 
no  immediate  danger  of  coma.  What  the  actual  conditions  are  in 
those  extremely  rare  cases  in  which  a  strong  acidosis  has  been 
found  as  a  result  of  the  presence  of  some  other  acid  than  /?-oxy- 
butj'-ric  (and  diacetic)  acid,  I  do  not  know. 

The  /3-oxybutyric  acid  in  the  urine  of  the  three  substances  under 
consideration  alone  reaches  large  amounts.  One  hundred  grams  in 
twenty-four  hours  is  not  very  rare  ;  seventy  grams  is  not  uncom- 
mon. Kiilz  found  226  grams  in  one  case.  The  relation  between 
the  quantity  of  /3-oxybutyric  acid  in  the  blood  and  the  quantity  in 
the  urine  is  not  clearly  knoAvn.  Hugonenq  found  0.427  per  cent, 
in  the  blood  and  0.448  per  cent,  in  the  urine.  In  the  enormous 
majority  of  cases  the  acid  diathesis — the  "  acidosis,"  as  Naunyn  calls 
it — are  determined  chiefly  by  the  amount  of  /3-oxybutyric  acid. 
This  danger  is  also,  and  to  a  great  extent,  determined  by  the 
general  state.  The  same  amount  of  acid  which  one  patient  is  able 
to  endure  for  months  may  kill  another  in  a  few  hours.  As  soon  as 
the  urine  for  twenty-four  hours  contains  as  much  as  twenty  grams 
of /3-oxybutyric  acid  there  may  be  danger  of  coma.* 

Diacetic  acid  is  found  throughout  the  whole  of  the  severe  stage 
and,  as  a  mere  diabetic  phenomenon,  not  in  the  mild  stage  at  all.  If 
a  healthy  person  be  given  an  exclusive  diet  of  proteids  or  of  proteids 
and  fat,  no  diaceturia  arises  so  long  as  a  sufficiently  large  number 
of  calories  for  the  nutritive  balance  is  ingested  ;  but  the  inges- 
tion of  a  sufficient  supply  of  calories  without  carbohydrate  in  the 
food  is  a  difficult  task.  A  deficit  readily  arises,  of  which  from  83 
to  93  per  cent,  is  covered  by  the  consumption  of  the  patient's  own 
fat,  while  the  remainder  is  furnished  by  that  of  his  own  proteids 
(Lusk,  Miura,  v.  Noorden).  With  this  kind  of  disintegration  of  the 
latter  diaceturia  begins  and  Gerhardt's  reaction  with  the  urine  will 
appear.  In  this  manner  diaceturia  will  arise  in  cases  of  mild  dia- 
betes, just  as  it  does  in  cases  of  ulcer  of  the  stomach  or  of  appen- 
dicitis or  of  seasickness  in  the  progress  of  more  or  less  pronounced 
starvation.     Unless  the  starvation  is  very  severe,  however,  the  solu- 


*  This  danger  can  also  be  estimated  by  the  amount  of  ammonia  excreted.  As  soon 
as  the  quantity  reaches  1.5  grams  in  twenty-four  hours  the  acidosis  is  sufficient,  in  con- 
junction with  a  greatly  enfeebled  general  state,  to  produce  coma. 


METABOLISM    AND    NUTRITIVE    NEEDS.  225 

tion  of  ferric  chlorid  will  not  cause  the  typical  purple  or  bluish-red 
color  to  appear  in  the  urine.  When  the  ferric  chlorid  falls  drop  by 
drop  into  the  urine,  it  becomes  surrounded  by  a  red  zone  ;  when  the 
phosphates  of  iron  afterward  sink,  the  liquid  above  has  a  brownish- 
red,  sherry  color. 

Even  in  the  worst  cases  the  diacetic  acid  in  the  urine  hardly  ever 
reaches  twenty  grams  in  the  twenty -four  hours,  and,  though  it  must 
be  considered  as  contributing  to  the  acidosis  and  to  the  coma,  it  is 
far  less  efficient  in  this  respect  than  the  /3-oxybutyric  acid. 

It  is  an  important  circumstance  that,  so  far  as  I  have  been  able 
to  ascertain,  the  whole  severe  stage  of  diabetes,  per  se  and  apart 
from  other  causes,  is  attended  with  diaceturia.  Whenever  I  see 
a  frank  Gerhardt's  reaction  with  the  urine  of  a  patient  receiving 
an  abundant  supply  of  calories  with  his  food, — which  generally 
presupposes  a  certain  amount  of  carbohydrate, — I  know  at  once 
that  an  exclusive  diet  on  meat  and  fat  will  not  remove  the  glucose 
from  his  urine.  On  the  other  hand,  the  absence  of  diacetic  acid 
from  the  urine  almost  invariably  indicates  that  the  case  is  still  in 
the  mild  stage,  and  that  a  number  of  days  *  of  abstinence  from  car- 
bohydrates will  cause  the  sugar  to  disappear  from  the  urine.  There 
are,  however,  exceptions  to  this  rule.  Also  with  regard  to  diacet- 
uria, it  is  known  that  there  are  individuals  living  on  the  border- 
land between  the  mild  and  the  severe  stage  of  diabetes.  I  have  seen 
patients  who,  with  an  abundant  supply  of  mixed  food,  presented  a 
large  quantity  of  the  glucose  in  the  urine,  but  no  diacetic  acid,  and 
who,  with  an  exclusive  but  quite  adequate  supply  of  meat  and  fat, 
continued  to  excrete  a  small  amount  of  glucose,  and  then  also  ex- 
hibited slight  diaceturia.  I  take  it  that  these  individuals  are  able 
with  an  abundant  supply  of  carbohydrates  to  protect  their  own  pro- 
teids  from  the  disintegration  that  at  once  gives  rise  to  both  glyco- 
suria and  diaceturia  ;  all  the  glucose  excreted  with  such  a  diet  being 
derived  from  carbohydrates.  When  carbohydrates  are  strongly 
diminished  or  excluded,  the  glycosuria  due  to  them  ceases,  but  the 
patient  is  no  longer  able  to  protect  his  own  proteids,  the  fat  being 

*  The  length  of  the  period  of  abstinence  from  carbohydrates  for  the  necessary  removal 
of  the  glucose  from  the  urine  varies  according  to  the  patient's  power  of  assimilation,  and 
probably,  also,  according  to  the  storage  of  glycogen  and  to  other  causes  of  an  unknown 

nature. 


226  DIABETES    MELLITUS    AND    GLYCOSURIA. 

less  efficient  for  this  purpose  than  carbohydrates.  He  excretes  only 
a  small  quantity  of  glucose,  but  this  is  now  derived  from  the  dis- 
integration of  his  own  proteids,  and  the  diacetic  acid  has  the  same 
origin. 

The  difficulty  of  demonstrating  the  presence  of  acetone  in  the 
urine,  and  the  still  greater  difficulty  of  determining  the  quantity 
produced  in  twenty-four  hours,*  have  given  rise  to  much  uncer- 
tainty with  regard  to  many  important  points  connected  with  this 
substance.  It  is  not  known  in  what  cases  of  diabetes  acetone,  as  a 
mere  diabetic  phenomenon,  is  abnormally  increased.  Unlike  diacetic 
and  /?-oxybutyric  acids,  acetone  is  also  found,  though  only  in  small 
quantities,  in  normal  urine.  It  is  certain  that  in  a  great  many  cases 
of  fully  developed  but  mild  diabetes  there  is  no  increase  of  acetone 
with  an  abundant  supply  of  carbohydrate.  Von  Jaksch  found  only 
the  normal,  small  quantity  of  acetone  in  cases  with  an  excretion  of 
from  250  to  300  grams  of  glucose.  On  the  other  hand,  it  seems 
probable  that  an  increased  amount  of  acetone  may  appear  in  the 
urine  in  mild  cases.  One  may  sometimes  perceive  a  faint  but  distinct 
odor  of  acetone  on  the  breath  of  patients  in  the  mild  stage,  even 
when  they  seem  to  be  receiving  a  supply  of  calories  sufficient  for  the 
maintenance  of  the  nutritive  equilibrium.  When  any  person,  dia- 
betic or  not,  excludes  carbohydrates  from  his  food  and  lives  on  meat 
and  fat,  the  amount  of  acetone  in  the  urine  always  increases  (Hirsch- 
berg  and  others).  This  occurs  more  readily  in  diabetics  than  in 
healthy  individuals  (Rosenfeld),  but  even  in  healthy  individuals  it 
may  cause  an  excretion  of  0.7  gram  in  the  twenty -four  hours.  The 
addition  to  the  food  of  sixty  grams  of  glucose  or  of  starch  causes 
the  acetonuria  to  disappear. f  The  excretion  of  acetone  in  the  urine 
is  certainly  of  smaller  significance  than  the  excretion  of  diacetic  or 
of  ,?-oxybutyric  acid.  If,  with  a  sufficient  supply  of  calories  from  a 
mixed  diet,  including  a  fair  amount  of  carbohydrates,  acetonuria 
exists  at  all  in  the  mild  stage,  this  certainly  must  occur  in  cases  not 
far  from  the  boundary  between  this  and  the  severe  stage. 

It  is  a  most  important  fact  that  the  whole  trio  of  acetone,  diacetic 


*  Acetone   being  constantly  exhaled   through   the  lungs,  the   determination   of   the 
quantity  excreted  necessitates  an  analysis  of  the  expired  air. 

f  Mannite  in  considerable  amounts  also  causes  acetonuria  to  disappear  (Hirschberg). 


METABOLISM    AND    NUTRITIVE    NEEDS.  22/ 

acid,  and  /3-oxybutyric  acid  seem  to  be  more  easily  produced  with 
an  exclusive  diet  of  fat  and  proteids  than  when  carbohydrate  is 
added.  Dr.  D.  Gerhardt  (see  Naunyn)  has  observed  that  the  same 
insufficient  supply  of  calories  in  the  diet  causes  the  appearance  of 
more  /3-oxybutyric  acid  in  the  urine  if  made  up  of  proteids  and  fat 
alone  than  if  derived  from  a  mixed  diet,  consisting  in  part  of  carbo- 
hydrates. Hirschberg  has  proved  the  analogous  fact  with  regard  to 
acetone,  and  the  same  is  probably  true  also  of  diacetic  acid.  It  is 
a  common  phenomenon  that  Gerhardt's  reaction  perceptibly  in- 
creases in  diabetic  urine  when  the  patient  is  deprived  of  carbohy- 
drates and  is  put  on  a  strict  animal  diet. 

Free  fatty  acids  (formic,  acetic,  butyric,  propionic,  valerianic), 
which  in  normal  urine  scarcely  reach  o.oi  gram  in  the  twenty-four 
hours,  may  in  cases  of  severe  diabetes  be  present  in  tenfold  quan- 
tity (Rumpf ).  These  acids  are  derivatives  of  proteids,  and  the  dia- 
betic aciduria,  as  has  been  already  mentioned,  is  a  feature  of  the 
severe  stage. 

The  whole  amount  of  acids — acetic,  /S-oxybutyric,  fatty  acids, 
lactic  acid,  oxalic  acid,  phosphoric  acid,  sulphuric  acid  (in  the 
sulphates  and  combined) — may  reach  a  large  quantity,  and  in  the 
course  of  twenty-four  hours  equal  forty  or  fifty  grams  of  concen- 
trated sulphuric  acid. 

The  acid  diathesis,  the  acidosis,  causes  an  increase  of  ammonia 
in  the  blood  and  the  urine  in  cases  of  severe  diabetes,  and  the 
quantity  in  the  urine,  which  normally  is  about  0.7  gram  for  twenty- 
four  hours,  may  reach  the  enormous  amount  of  twelve  grams  in 
cases  of  diabetes  (Stadelmann).  This  shows  the  great  variation  in 
the  individual  ability  to  bear  up  under  the  acidosis  and  to  resist  its 
comatose  influence  ;  even  1.5  grams  of  ammonia  constitute  a  warn- 
ing of  coma,  and  two  grams  are  often  quite  a  distinct  forerunner  of 
it. 

When  in  a  severe  case  of  diabetes  the  carbohydrates  are 
restricted  or  are  excluded,  autophagy  and  loss  of  bodily  weight 
increase  ;  glycosuria  and  generally  polyuria  diminish  ;  the  urine, 
even  when  diluted  to  its  previous  volume,  yields  a  more  pronounced 
Gerhardt's  reaction,  from  the  presence  of  an  increased  amount  of 
diacetic  acid  ;  and  the  polarimeter  shows  some  increase  in  the  excre- 
tion of /5-oxybutyric  acid.      Sometimes,  in  cases  that  had  previously 


2  28  DIABETES    MELLITUS   AND    GLYCOSURIA. 

been  free  from  albuminuria,  one  also  finds  that  with  the  strict  diet 
the  urine  begins  to  contain  a  small  amount  of  albumin,  probably 
from  the  effect  of  the  acid  toxins  on  the  kidneys. 

There  are  in  the  hterature,  and  especially  from  those  who  defend  exclusion  of 
carbohydrates,  even  in  the  severe  stage,  reports  of  a  decrease  of  diaceturia  with 
such  a  dietetic  change.  Thus,  Troye  *  relates  the  case  of  a  patient  who,  with 
mixed  diet,  excreted  658  grams  of  glucose  and  a  moderate  amount  of  diacetic 
acid  in  more  than  nine  liters  of  urine  in  the  twenty-four  hours,  but  who,  after  five 
days  of  a  strict  diet,  excreted  a  normal  amount  of  urine,  free  from  diacetic  acid, 
but  containing  twenty-seven  grams  of  glucose.  Such  a  statement  is  so  contra- 
dictory to  all  of  my  experience  that  I  can  only  conclude  that  there  must  be 
some  mistake. 

Stokvis  seems  to  consider  the  occasional  appearance  of  albumin  in  the  urine 
after  the  exclusion  of  the  carbohydrates  from  the  diet  as  resulting  from  the 
decrease  in  the  quantity  of  urine,  so  that  a  trace,  previously  undiscoverable, 
becomes  appreciable  with  Heller's  nitric-acid  test.  Even  after  diluting  the 
urine  to  its  previous  volume  one  finds  sometimes,  with  a  marked  restriction  of 
carbohydrates,  a  trace  of  albumin  that  did  not  appear  previously. 

Azotiiria  f  in  cases  of  diabetes  has  been  much  spoken  of.  An  in- 
creased amount  of  nitrogen  may  appear  constantly  in  the  urine  in 
cases  of  diabetes  from  two  entirely  different  causes.  There  may  be 
an  alimentary  azotiiria  and  a  protoplasmic  or  toxic  azotiiria. 

Alimentary  azotiiria  of  diabetes  is  easy  to  understand,  and  is  the 
only  increased  excretion  of  nitrogen  in  the  mild  stage.  The  dia- 
betic patient  either  ingests  much  less  carbohydrate  with  his  food  or 
he  again  loses  part  of  it  in  his  urine,  and  he  must  make  up  for 
this  by  the  ingestion  of  a  larger  amount  of  fat  and  proteids.  The 
larger  supply  of  proteids  to  a  diabetic  as  to  a  healthy  person  neces- 
sarily leads  to  a  larger  excretion  of  nitrogen.  This  excretion  may 
be  temporarily  increased  in  consequence  of  marked  polydipsia  and 
polyuria,  which  per  sc  may  for  the  moment  increase  the  nitrogen 
in  the  urine.  During  somewhat  longer  periods,  however,  with  suf- 
ficient food,  the  amount  of  nitrogen  excreted  in  a  case  of  diabetes  in 
the  mild  stage  does  not  exceed  the  amount  of  nitrogen  ingested. 

The  second  variety  of  diabetic  azoturia,  toxic  or  protoplasmic  azo- 

*  "  Archiv  fiir  experim.  Path,  und  Pharm.,"  1890. 

f  Among  one  hundred  cases  Bouchard  found  forty-seven  with  an  ordinarily  large 
amount  of  nitrogen  in  the  urine,  forty  with  an  increased  amount,  and  thirteen  with  a 
diminished  amount.  Such  figures  are  not  worth  much,  if  they  do  not  cover  a  considerable 
length  of  time. 


METABOLISM    AND    NUTRITIVE    NEEDS.  229 

turia,  is  a  feature  of  the  severe  stage  exclusively  ;  but  it  has  not  yet 
been  quite  decided  whether  it  occurs  in  all  or  only  in  advanced 
cases  of  this  stage.  Toxic  azoturia,  however,  was  known  to  Ber- 
nard, and  was  subsequently  studied  by  Voit  and  Pettenkofer, 
Kiilz,  V.  Mering  and  Minkowski,  Chauveau  and  Kaufmann,  Gley, 
Thiroloix,  and  others.  It  is  believed  to  be  caused  by  the  toxins, 
and  chiefly  by  the  acid  toxins,  in  the  blood,  and  their  disintegrating 
influence  on  protoplasm.  The  most  marked  effect  of  this  kind  un- 
doubtedly is  caused  by  /3-oxybutyric  acid.  For  my  part,  I  am 
inclined  to  believe  that  some  toxic  disintegration  of  protoplasm 
takes  place  throughout  the  whole  of  the  severe  stage,  and  that  there 
is  a  slight  toxic  azoturia  even  in  cases  in  which  the  /?-oxybutyric  acid 
has  not  yet  shown  itself,  a  purely  diabetic  diaceturia  being  already  a 
sign  of  toxic  or  protoplasmic  disintegration.  It  will  be  no  easy 
matter,  however,  to  demonstrate  in  such  cases  a  constant  excess  of 
nitrogen-excretion  over  nitrogen-ingestion.  This  seems  to  me, 
however,  to  have  been  fully  done  in  dogs  after  total  extirpation 
of  the  pancreas,  and  I  consider  unsustained  the  doubt  remaining 
in  some  minds  as  to  the  very  existence  of  a  diabetic  toxic  dis- 
integration of  tissue  and  the  consequent  azoturia. 

During  coma  the  products  of  metabolism  in  the  urine  generally 
decrease.  Miinzer  and  Strasser,  however,  observed  the  nitrogen 
increase. 

The  present  views  on  diabetic  azoturia  have  been  gradually  developed  by 
the  labors  of  Hosier,  Boecker,  Thierfelder,  Uhle,  Reich,  Rosenstein,  Haugh- 
ton,  and  Gathgens  (1853-1866),  and  within  more  recent  years  by  the  researches 
of  Kiilz,  Kratschmer,  Pettenkofer  and  Voit,  Frerichs,  Lusk,  Fr.  Voit,  Minkow- 
ski, V.  Mering,  v.  Noorden,  Weintraud,  Borchert  and  Finkelstein,  Gley,  Thiro- 
loix, and  others. 

The  enormous  amounts  of  animal  food  consumed  by  some  diabetic  patients 
sometimes  cause  the  appearance  of  large  quantities  of  nitrogen  in  the  urine. 
Leube  found  150  grams,  Fiirbringer  163  grams  of  urea,  and  I  found  eighty 
grams  of  nitrogen  (equal  to  171  grams  of  urea  ;  from  13  to  16  per  cent,  of  the 
nitrogen,  however,  belongs  to  other  substances)  in  twenty-four  hours.  Such 
figures  are  rare,  but  large  quantities  of  nitrogen  in  the  urine  are  common  in 
cases  of  diabetes.  This  fact  favored  the  opinion  that  every  diabetic  patient 
excreted  more  nitrogen  than  he  ingested,  an  opinion  which  for  a  long  time 
prevailed,  though  the  very  analyses  on  which  it  was  founded  and  the 
mathematic  absurdities  to  which  it  leads,  considering  the  average  duration  of 
life  in  mild  cases  of  diabetes,  ought  to  have  led  quickly  to  more  rational  views. 

It  is   evident  that   if  a  diabetic  and  a  healthy  individual  ingest  the  same 


230  DIABETES    MELLITUS    AND    GLYCOSURIA. 

number  of  calories  with  their  food,  and  the  diabetic  again  loses  a  certain 
amount  of  them  in  the  form  of  glucose  in  his  urine,  the  food  that  is  barely 
sufficient  for  the  healthy  individual  will  not  be  sufficient  for  the  diabetic,  and 
the  latter  will  cover  the  deficit  by  expending  a  part  of  his  own  fat  and  a  smaller 
part  of  his  own  proteids.  He  will  then  decrease  in  bodily  weight,  and  his 
urine  will  contain  more  nitrogen  than  has  been  ingested  and  digested.  The 
same  would  happen  with  the  healthy  individual  if  from  his  food  were  removed 
the  number  of  calories  represented  by  glucose  in  the  diabetic's  urine.  If, 
however,  both  individuals  received  the  same  amount  of  calories  with  a  diet 
that  permits  the  diabetic  to  utilize^the  whole  amount,  he  will  not,  in  the  mild 
stage,  excrete  more  nitrogen  than  the  healthy  individual. 

In  the  severe  stage  toxic  disintegration  of  protoplasm  is  a  priori  not  improb- 
able, and  it  seems  almost  impossible  to  explain  the  results  of  recent  most 
laborious  investigations  without  admitting  its  occurrence. 

It  is  not  at  all  certain  that  even  all  of  the  common  toxins  in  cases  of  diabetes 
are  known  at  present,  though  those  that  are  amply  explain  the  comatose  syn- 
drome. Then,  just  as  there  are  instances  in  which  levulose  appears  in  the 
urine  instead  of  the  customary  saccharid,  glucose,  there  may  be  exceptional 
products  of  metabolism.  In  fact,  the  more  one  studies  diabetes,  the  more  will 
he  be  prepared  for  surprises.  We  must,  therefore,  not  entirely  close  our  minds 
against  the  possibility  of  correct  observation  in  Rupstein's  (1874)  and  Kiilz's 
(1875)  cases  of  diabetes  in  which  alcohol  was  excreted  in  the  urine.  It  is 
impossible  to  presume,  in  either  case,  the  occurrence  of  fermentation  in  the 
bladder,  and  there  scarcely  remains  any  other  way  of  explaining  the  formation 
of  alcohol  than  by  accepting  Rupstein's  theory  of  an  oxidation  of  diacetic  acid. 
Kiilz,  who  was  about  as  skeptical  as  any  right-minded  person  is  justified  in 
being,  considered  that  the  large  amount  of  alcohol  in  the  urine  was  proved  in 
the  case  that  he  pubhshed.  Still,  he  did  not  observe  it  himself;  but  Dr. 
Guckelberg,  an  assistant  of  Liebig's,  performed  the  analytic  work.  The 
patient  died  (in  coma)  in  1869,  shortly  after  exhibiting  symptoms  of  alcoholic 
intoxication,  but  before  the  reactions  of  the  substances  chiefly  concerned  were 
as  well  known  as  they  are  now ;  and  incipient  diabetic  coma  may  sometimes 
resemble  alcoholic  intoxication. 

The  diabetic  patient  using  an  abundance  of  animal  food  ingests  a 
large  amount  of  salts.  Lean  meat  contains  about  0.70  per  cent, 
of  phosphoric  acid,  and  diabetic  phosphatnria  may  be  four  times  as 
marked  as  the  normal  phosphaturia.  Whatever  future  researches 
may  have  to  add  to  our  present  views  on  the  functions  and  influence 
of  mineral  salts  in  the  organism,  the  question  that  chiefly  interests 
us  here  is  whether  or  not  the  component  salts  of  the  bones  are  found 
in  the  urine  in  cases  of  severe  diabetes  in  larger  quantities  than  can 
be  explained  by  the  quantity  of  salts  ingested  plus  the  protoplasmic 
disintegration  of  the  soft  cellular  tissues  almost  universally  admitted 
as  taking  place  in  such  cases.     Calcium  and  magnesium  phosphate 


METABOLISM    AND    NUTRITIVE    NEEDS.  23 1 

and  the  other  salts  that  enter  into  the  constitution  of  the  bones  are 
excreted  in  such  large  amounts  in  some  cases  of  severe  diabetes 
that  many  writers  in  explanation  suggest  the  existence  of  osteo- 
inalacia  as  a  result  either  of  the  acidosis  or  of  trophoneurotic  influ- 
ences. The  question  has  not  yet  been  decided,  and  Dr.  E.  Ten- 
baum's  recent  researches  only  prove  what  an  enormous  amount  of 
elaborate  work  will  be  required  for  its  solution. 

The  water  streaming  constantly  through  the  organism,  with  most 
important  functions  and  effects  (of  which  there  is  yet  much  to  learn), 
is  generally  increased  in  cases  of  diabetes.  Even  normally  the  figures 
are  large.  About  sixty-three  per  cent,  of  the  human  body  consists 
of  water.  A  man  of  ordinary  size  ingests  about  2.5  or  3  liters 
daily,*  and  excretes  an  equal  amount.  About  one-third  of  the 
whole  excretion  passes  through  the  lungs  and  the  skin,  and  the 
greater  part  of  the  remainder  is  eliminated  with  the  excreta  and 
feces,  chiefly  in  the  urine,  and  only  a  comparatively  small  part 
in  other  excretions.  In  cases  of  diabetes  the  increased  ingestion  of 
water  causes  chiefly  an  increase  in  the  amount  of  urine.  The  elimi- 
nation through  lungs  and  the  skin  is  usually  diminished,  partly  on 
account  of  atrophy  of  the  latter,  partly  on  account  of  the  increased 
amount  of  sugar  in  the  blood,  which  retains  the  water  more  firmly 
than  normally. 

Ever  since  1580  some  persons,  in  their  amazement  at  the  enormous  quantity 
of  urine  sometimes  passed  in  cases  of  diabetes,  have  held  the  curious  notion  that 
a  diabetic  patient  may  pass  more  urine  than  he  ingests  water,  and  even  Gath- 
gens,  in  1886,  beheved  that  he  had  proved  this  astounding  fact,  which  could 
scarcely  be  explained  otherwise  than  upon  the  theory  that  a  diabetic  patient, 
like  concentrated  sulphuric  acid,  attracts  to  himself  the  water  in  the  air.  This 
would  have  to  be  done  by  the  so-called  "  negative  insensible  perspiration  " — one 
of  the  most  amusing  products  of  speculative  science.  [The  positive  insensible 
perspiration  is  obtained  by  weighing  a  person  at  the  beginning  and  at  the  end 
of  the  experiment,  by  adding  the  weight  of  the  ingested  water  to  the  first  and 
of  the  excreted  water  to  the  last  figure ;  the  difference  between  the  two  sums 
then  represents  the  "insensible  perspiration."]  Burger,  Nasse,  Kulz,  and 
Engelmann  have  put  an  end  to  all  these  fanciful  theories  by  showing  that 
during  somewhat  extended  periods  no  more  water  is  excreted  in  cases  of  dia- 
betes than  is  ingested.  The  insensible  perspiration  in  severe  cases  is  undoubt- 
edly diminished. 

*  According  to  Forster,  from  2200  to  3500  cu.  cm. 


232  DIABETES    MELLITUS    AND   GLYCOSURIA. 

A  diabetic  needs  in  general  the  same  amount  of  digested  and 
utilized  calories  as  a  normal  individual.  This  was  proved  by  Pet- 
tenkofer  and  Voit,*  and  has  been  corroborated  by  Fr.  Voit,  Wein- 
traud,  Pautz,  Borchert  and  Finkelstein,  and  other  investigators. 

According  to  Rubner,  a  normal  man  requires  in  twenty-four 
hours  per  kilogram  of  bodily  weight  : 

Inrepose, 32.9  calories. f     With  moderate  work,    .    .    .  41  calories. 

With  light  workjj    .    .  34.9      "  With  severe  work,    ....  48        " 

The  thin  individual,  richer  in  cells,  requires  more  calories  than 
the  fat  one,  with  more  comparatively  inactive  adipose  tissue.  The 
growing  child,  with  a  larger  bodily  surface  compared  to  its  weight, 
requires  more  than  a  developed  person. 

One  gram  of  carbohydrate  represents  gross  4.1  calories,  net  3.8.^ 
"  fat  "  "       9.3       "  "    8.4. 

"       "  proteids  "  "      4.1       "  "    3.2. 

The  figures  for  the  gross  value  are  Rubner's,  those  for  the  net 
value  are  v.  Rechenberg's,  who  estimated  the  average  loss  from  the 
amount  of  the  ingested  (but  undigested)  food  in  the  feces.  This 
loss  usually  is  not  greater  in  diabetics  than  in  normal  individuals, 
but  it  is  probably  somewhat  smaller  than  it  was  in  v.  Rechenberg's 
weavers,  who  doubtless  received  rather  coarse  food. 

The  alcohol  represents  gross  seven  calories,  and  the  net  value 
may,  in  view  of  the  small  daily  doses,  be  put  practically  at  the  same 

*  The  learned  Professors  Pettenkofer  and  Voit,  however  splendid  their  life's  work, 
unfortunately  were  sometimes  a  little  absent-minded.  Thus,  when  in  1867  they  made 
their  observations  upon  an  unusually  small  diabetic  Teuton,  weighing  only  54  kilograms, 
they  at  first  overlooked  the  fact  that  he  could  not  be  expected  to  eat  as  much  and  to 
consume  as  much  oxygen  and  produce  as  much  carbonic  acid  as  an  ordinary  Teuton ; 
and  from  the  low  figures  they  gained  the  impression  that  the  metabolism  was  decreased. 
In  relation  to  the  bodily  weight,  however,  their  man  consumed  a  perfectly  normal 
amount  of  calories, — 34.5  calories  per  kilogram  of  bodily  weight  in  twenty-four  hours, 
during  repose,  in  the  apparatus  used.  All  subsequent  figures,  correctly  interpreted,  lead 
to  the  same  result.      (Livierato's  researches  can  not  be  considered  satisfactory.) 

-f  I  always  mean  great  calories,  viz. ,  the  amount  of  heat  required  to  raise  the  temper- 
ature of  one  kilogram  of  water  I  °  C. 

j  Only  mechanic  (and  chemic)  work  entails  expenditure  of  force.  Nature  is  too 
generous  to  charge  us  for  our  poor  intellectual  work. 

§  Rubner's  figures  are  : 

4. 116  calories  for. starch.     3.877  calories  for lactose. 

3.959  "  ....  cane-sugar.     3.692         "  glucose. 


METABOLISM    AND    NUTRITIVE    NEEDS.  233 

figure.  The  levulose,  an  important  alimentary  item  in  cases  of  dia- 
betes, represents  about  3.7  calories  gross,  and  nearly  as  much  net, 
the  amount  taken  being  almost  entirely  absorbed. 

It  must  be  borne  in  mind  that  the  isodynamic  law  is  to  be  accepted 
with  some  reservation,  and  that  different  kinds  of  food  are  not  inter- 
changeable with  regard  to  the  number  of  calories  they  represent. 
The  same  number  of  calories  derived  from  carbohydrates  are  more 
efficient  in  protecting  the  proteids  of  the  organism  than  the  calories 
derived  from  fats,  and  the  latter  rank  higher  in  this  respect  than  the 
calories  derived  from  alcohol.  Then,  it  seems  to  me  that  diabetics, 
especially  when  subjected  to  rigorous  restriction  of  carbohydrates, 
sometimes,  though  unfortunately  only  for  a  short  while,  apart 
from  the  calories  lost  by  glycosuria,  consume  an  amazingly  large 
amount  of  calories.  I  have  seen  the  value  utilized  reach  nearly  one 
hundred  calories  per  kilogram  of  bodily  weight  in  twenty-four  hours. 
The  toxic  disintegration  of  protoplasm  in  severe  cases  explains  this 
phenomenon  in  part.  In  other  part  it  may  be  explained  by  the 
increased  work  necessary  for  the  mere  transformation  of  other 
molecular  structures  into  glucose.  Still,  I  do  not  feel  at  all  certain 
that  we  know  at  present  in  every  detail  how  to  estimate  dietic 
values  for  our  diabetic  patients. 

To  estimate  the  caloric  value  of  a  patient's  food  we  must  weigh 
all  that  he  ingests  and  obtain  the  net  value  of  the  total.  So'  far  as 
proteids  are  concerned,  we  can  take  the  easier  way  of  determining 
the  nitrogen  in  the  urine.  Albumin  consisting  of  sixteen  per  cent, 
nitrogen,  the  ingested  and  digested  albumin  can  be  determined  in 
grams  by  multiplying  the  number  of  grams  of  nitrogen  in  the  urine 
by  '^-^  (=  6.25).  (We  then  presume  that  practically  all  of  the 
nitrogen  has,  as  usual,  been  ingested  in  the  form  of  proteids,  and  we 
take  no  account  of  the  toxic  disintegration  of  the  tissues,  which  is  a 
feature  only  of  severe  cases,  and  usually  gives  rise  to  the  ap- 
pearance of  comparatively  small  amounts  of  nitrogen  in  the  urine, 
and  which  can  not  be  determined  without  an  immense  amount  of 
analytic  work.)  In  using  this  mode  of  calculation  we  must,  of 
course,  value  each  gram  of  proteid  at  4.  i  calories.  From  the  final 
sum  of  calories  derived  from  proteids,  fats,  carbohydrates,  and 
alcohol  we  then  subtract  the  number  of  calories  lost  in  the  urine  in 
the  form  of  glucose,  valued  at  3.7  calories  per  gram. 
16 


2  34  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Mr.  R.  has  drunk  0.5  liter  of  milk  with  17.5  grams  of  proteid,  18  grams  of 
fat,  and  24  grams  of  lactose  ;  which  represent  in  calories  17.5  X  3-2  +  18  X 
8.4  +  24  X  3-8  =  298.4.  He  had  had  650  grams  of  raw  meat,  with  about  20 
per  cent,  of  proteids  and  6.5  per  cent,  of  fats  and  a  net  value  of  416  +  354.9 
=  770.9  calories.  Four  eggs  may  be  considered  as  representing  280  calories. 
Two  hundred  grams  of  butter  (with  1.6  grams  of  proteid,  166  grams  of  fat,  and 
0.4  grams  of  carbohydrate)  represent  1394.6  calories  ;  100  grams  of  rye-bread, 
209.84  calories;  50  grams  of  rich  cheese  yielded  13  grams  of  proteids  +  15 
grams  of  fat  +  1.25  grams  of  carbohydrate  =  172.2  calories.  Sixty  grams  of 
American  whisky  represent  about  219  calories.  No  account  was  taken  of  some 
tomatoes  and  some  "  sauerkraut."  If  I  am  correct  in  my  calculations — and  of 
this  I  am  not  certain — R.  received  298.4  +  770.9  +  280  +  1304.6  +  209.84  + 
172.3  +  219  =  3345.  Mr.  R.,  again,  lost  51.8  calories  in  14  grams  of  glucose 
in  the  urine,  and  thus  really  received  only  3263.2 — i.  e.,  a  trifle  more  than  40.3 
calories  per  kilogram  of  his  bodily  weight,  which  was  82  and  was  increasing. 

Mr.  L.  had  excreted  31  grams  of  nitrogen,  and  had  thus  utilized  62.5  X  3' 
:=  193.75  grams  of  proteid,  or  4.1  X  193-75  =  793-3  calories.  About  180 
grams  of  fat  had  yielded,  net,  1512  calories.  Ninety  grams  of  white  bread  had 
yielded  179.18  calories.  Twenty  grams  of  alcohol  had  yielded  140  calories. 
The  man  had  lost  32  grams  of  glucose,  or  1 18.4  calories.  He  had  thus  utilized 
2624.48 —  1 18.4  =  2506.08  calories.  He  weighed  68  kilograms,  had  received 
over  36.8  per  kilogram,  did  not  perform  much  work,  and   increased  in  weight. 


These  calculations,  however,  are  troublesome,  and  will  not  be 
undertaken  in  addition  to  the  strain  of  practical  work.  It  is  easy, 
however,  to  remember  that  soft,  white  bread  usually  yields  about 
twice  as  many  calories  as  its  own  weight  in  grams  ;  that  an  egg 
represents  about  70  or  75  calories;  that  raw,  lean  meat  yields  a 
somewhat  larger,  raw,  lean  fish  a  somewhat  smaller,  number  of 
calories  than  its  own  weight  in  grams  ;  that  butter  yields  about  7 
calories  per  gram,  and  alcohol  also  7  calories  per  gram.  All  of 
these  figures  represent  the  net  value,  and  are  all  that  the  prac- 
titioner need  bear  in  mind  when  confronted  with  the  important  task 
of  informing  his  patient  as  to  the  necessary  amount  of  food  to  be 
ingested. 

The  oxygen  consumed  and  the  carbonic  acid  generated  in  cases 
of  diabetes  equal  normal  quantities.  Except  what  is  represented  by 
the  glucose  in  his  urine  and  by  diabetic  toxins,  the  diabetic  patient 
oxidizes  his  food,  especially  the  sometimes  enormous  quantities  of 
fat,  as  a  normal  person  does,  just  as  he  oxidizes  organic  acids 
(Strauss),  or  lactates  (Weintraud),  or  benzol  (v.  Nencki  and  Sieber), 
etc.     The  normal   consumption  of  oxygen  varies  from   3   to  4.5 


METABOLISM    AND    NUTRITIVE    NEEDS.  235 

cu.  cm.,  and  is,  on  the  average,  3.81  cu.  cm.  per  kilogram  of  bodily 
weight  in  the  minute.  The  amount  of  carbonic  acid  excreted,  esti- 
mated on  the  same  basis,  varies  from  2.5  to  3.5  cu.  cm.,  and  is,  on 
the  average,  3.08  cu.  cm.  The  figures  that  Leo  *  and  others  have 
found  in  cases  of  diabetes  correspond  exactly  with  these  figures. 

Since  Reignault's  and  Reiset's  classic  researches  it  has  been  known 
that  the  relation  between  the  oxygen  consumed  and  the  carbonic 
acid  excreted  varies  somewhat,  for  evident  chemic  reasons,  ac- 
cording to  the  nature  of  the  food,  so  that  the  respiratory  quotient, 
or  consumed'^o"'  ^^^i^^g  the  ingestion  of  food  consisting  essentially  of 
carbohydrates  approaches  the  quantity  i .  If  proteids  make  up  the 
greater  part  of  the  food,  the  figure  is  about  0.73.  When  large  quan- 
tities of  fat  exclusively  are  taken,  the  quotient  falls  somewhat,  and  is 
about  o./o.f  It  is  evident  that  the  quotient  in  diabetes  approaches 
in  general  the  latter  values,  the  patient  not  being  able  fully  to 
utilize  the  digested  carbohydrates,  J  and  that  it  is  the  farther  from 
the  ordinary  maximum  value  of  i  the  less  carbohydrate  oxidized, 
whether  this  arises  from  restriction  of  supply  or  from  a  low  limit  of 
the  power  of  assimilation.  Laves'  and  Weintraud's  researches  show, 
however,  that  a  diabetic  patient  on  an  exclusive  diet  of  meat  and  fat 
has  the  same  respiratory  quotient  as  a  normal  person  on  the  same 

*"Zeitschr.  f.  klin.  Med.,"  Berlin,  1891,  Supplement. 

f  Laulanie  found  that  in  starvation  both  the  respiratory  quotient  and  the  production  of 
heat  are  at  their  lowest.  With  an  exclusive  supply  of  meat  (muscles)  both  the  produc- 
tion of  heat  and  the  respiratory  quotient  increase.  Both  figures  in  the  latter  become 
higher,  but  the  increase  in  the  amount  of  carbonic  acid  excreted  is  rather  greater  than 
that  of  the  oxygen  excreted.  The  quotient,  however,  still  remains  comparatively  small. 
With  an  almost  exclusive  supply  of  carbohydrates  the  quotient  increases  considerably  and 
may  exceed  the  figure  I.  The  thermic  curve  follows  the  curve  of  the  absorption  of 
oxygen.  A  considerable  part  of  the  carbonic  acid  is  produced  without  the  generation  of 
heat  by  the  transformation  of  carbohydrate  into  fat. 

J  Laves  and  Weintraud,  from  the  results  of  their  investigations,  have  reached  the 
conclusions  that  in  cases  of  diabetes  the  ingested  carbohydrates,  even  apart  from  what 
is  lost  a£  glucose  in  the  urine,  do  not  give  rise  to  the  production  of  fully  as  much  car- 
bonic acid  as  in  normal  individuals,  probably  because  a  larger  part  of  the  carbohydrates 
remains  in  cases  of  diabetes  at  a  lower  point  of  oxidation  ;  e.g.,  as  oxalic  acid  instead  of 
forming  water  and  carbonic  acid. 

Henriot,  Magnus-Levy,  and  Bleibtreu  also  found  that  with  an  abundant  and  exclusive 
supply  of  carbohydrates  the  amount  of  carbonic  acid  excreted  may  attain  a  higher  figure 
than  the  amount  of  oxygen  consumed,  so  that  the  respiratory  quotient  exceeds  the  figure 
I,  and  may  even  reach  1.3. 


236  DIABETES     MELLITUS    AND    GLYCOSURIA, 

diet,  and  Leo's  figures  of  this  quotient  make  it  evident  that  even  in 
very  severe  cases  of  diabetes  with  a  mixed  diet  a  part  of  the  carbo- 
hydrates must  have  been  utilized  and  then  excreted  as  carbonic 
acid. 


CHAPTER  VIII.— INVESTIGATION  OF  A  CASE  OF  DIABETES. 

It  is  the  duty  of  every  physician  to  test  his  patient's  urine  for 
sugar.  This  investigation  alone  enables  us  to  detect  a  simple,  but 
rarely  insignificant,  habitual  glycosuria,  and  the  presence  of  sugar 
in  the  urine  may  be  the  one  distinctive  symptom  of  a  mild  but  true 
diabetes. 

In  making  this  test  two  most  important  points  must  be  observed. 
In  testing  there  should  be  used,  systematically,  a  sample  of  the 
urine  likely  to  contain  the  maximum,  or  nearly  the  maximum,  per- 
centage of  sugar  excreted  during  the  twenty-four  hours,  and  the 
test  should  be  so  performed  as  to  reveal  the  minimum  distinctly 
pathologic  quantity  of  glucose  in  the  urine. 

There  are,  as  we  have  seen,  a  great  many  individuals  with  a 
lowered  power  of  assimilating  carbohydrates  who  secrete  glucose 
only  for  short  periods  in  the  day,  some  time  after  meals,  and  then 
only  in  small  quantities.  Even  true  diabetics  in  the  mild  stage  are 
often,  even  apart  from  diet,  free  from  glycosuria  for  some  parts  of 
the  twenty-four  hours,  especially  in  the  morning  before  the  first 
meal. 

Tlie  first  and  most  important  rule  is,  tliercfore,  never  to  use  for 
a  test  a  specimen  of  urine  passed  when  the  patient's  stomach  is 
empty,  before  the  first  meal  of  the  day. 

The  best  means  of  deciding  from  a  single  examination  of  the  urine 
whether  a  person  is  normal  or  not  in  this  respect  is  furnished  by  a 
sample  passed  an  hour  after  the  end  of  the  dimier.  In  cases  of  sim- 
ple glycosuria  the  excretion  at  this  time  is,  with  rare  exceptions, 
near  its  maximum.  The  bladder  should  be  emptied  just  before  the 
meal,  which   ought   to   be   a   mixed  and  abundant   one,  including 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  237 

meat,  fat,  bread,  potatoes,  rice,  and  sweets,  but  not  any  consider- 
able quantity  of  alcoholic  liquors. 

The  patient  must  be  in  his  ordinary  state  ;  the  sample  of  urine 
ought  not  to  be  taken  during  any  illness  or  indisposition  or  after 
violent  emotion  or  excess  of  any  kind. 

For  the  purpose  of  revealing  with  certainty  the  presence  of  patho- 
logic traces  of  glucose,  the  practitioner  will  do  well  to  use  con- 
stantly two  different  reduction-tests,  and  to  verify  the  saccharine 
nature  of  the  reducing-substance  by  the  fermentation-test  whenever 
doubt  exists.  The  best  reagents  known  for  this  purpose  are  Ny- 
lander's  solution  of  bismuth  and  Trommer's  test,  used  in  a  some- 
what modified  way  with  Fehling's  solution  of  copper.* 

The  test  with  Nylander's  solution  is  the  easiest  to  perform  and 
to  observe.  A  tube  is  filled  one-fourth  or  one-third  with  urine,  and 
one-tenth  or  one-fifth  as  much  of  Nylander's  solution  is  added,  the 
mixture  being  boiled  for  four  or  five  minutes.  It  is  important  to  boil 
for  the  full  length  of  time.  Under  these  conditions  urine  containing 
at  least  some  tenths  of  a  per  cent,  of  glucose  will  be  rendered  more 
or  less  opaque  and  black ;  urine  containing  only  0.02  or  0.03  per 
cent,  will  assume  a  somewhat  brownish  color,  in  consequence  of 
admixture  of  the  reduced  bismuth  with  the  flakes  of  phosphates, 
etc.  Urine  containing  no  sugar,  or  less  than  0.02  per  cent.,  will, 
except  in  rare  cases,  maintain  its  transparency  and  its  yellow  color  ;  f 
the  latter  will  perhaps  be  somewhat  deepened. 

Trommer's  test,  as  is  known,  has  undergone  many  modifications, 
and  may  be  performed  in  several  different  ways.  I  have  adopted 
Worm-Miiller's  modification  in  part,  and  like  to  combine  it  with  the 
decoloration  of  the  urine  by  filtering  it  through  well-pulverized  and 


*  Both  of  these  tests  are  much  easier  and  quicker  of  performance  than  Fischer's  test, 
and  are,  when  only  hundredths  of  a  per  cent,  of  glucose  are  concerned,  at  least  as  re- 
liable. Fischer's  test,  as  is  well  known,  consists  in  heating  (over  a  water-bath)  for  about 
half  an  hour  about  fifty  parts  of  urine,  to  which  have  been  added  one  part  of  phenyl- 
hydrazin  chlorate  and  two  parts  of  sodium  acetate ;  the  characteristic  yellow  crystals  ol 
glycosazone  form  in  cooling.  Even  when  pure  phenylhydrazin  is  used  the  test — which 
also  yields  similar  crystals  with  other  saccharids  than  glucose — yields,  when  0.02  per  cent, 
or  smaller  quantities  of  glucose  are  present,  imperfect  crystals,  not  with  certainty  to  be 
distinguished  from  similar  formations  due  to  pentoses  (E.  Holmgren)  or  glycuronic  acids 
(except  by  their  melting  at  205°  €.—401°  F.)  (Thierfelder,  Geyer). 

")■  Apart  from  the  white  flakes  of  the  phosphates. 


238  DIABETES    MELLITUS   AND    GLYCOSURIA. 

well-washed  animal  charcoal.  In  one  tube  I  put  a  few  cubic  centi- 
meters of  the  urine  and  in  another  about  the  same  amount  of  Feh- 
ling's  solution.  The  latter  is  then  diluted  with  two  or  three  times 
its  volume  of  water,  and  the  contents  of  both  tubes  are  simulta- 
neously heated  to  boiling.  As  soon  as  they  are  fairly  boiling  I  let 
them  cool  for  twenty-five  seconds,  the  temperature  falling  to  70°  or 
75°  C.  (158°  or  167°  F.).*  I  then  slowly  pour  the  urine  into  the 
other  tube  ;  reduction  will  take  place  within  five  or  ten  minutes  if  the 
urine  contain  at  least  0.0 1  or  0.02  per  cent,  of  glucose.  By  following 
Worm-Miiller's  directions  closely,  and  especially  by  determining 
experimentally  the  best  possible  quantitative  relations  between 
the  solution  and  the  urine,  one  may  somewhat  improve  the  test, 
which,  however,  performed  in  the  manner  just  described,  is  delicate 
enough  for  practical  purposes  and  consumes  but  a  short  time. 

I  sometimes  perform  the  test  by  passing  not  too  small  a  quantity 
of  urine  through  animal  charcoal  on  the  filter,  then  washing  the 
charcoal  with  a  small  quantity  of  water,  diluting  one  volume  of 
Fehling's  solution  with  two  or  three  volumes  of  this  water,  and 
heating  to  the  boiling-point. 

In  whatever  manner  the  reduction-test  is  performed,  it  is  absolutely 
necessary,  in  cases  at  all  doubtful,  to  verify  the  saccharine  quality 
of  the  reducing-substances  by  the  fermentation-test.  To  this  end  a 
small  piece  of  yeast  is  placed  in  a  tube  almost  filled  with  urine,  which 
is  permitted  to  stand  at  ordinary  room-temperature  or  in  a  some- 
what warmer  place.  If  after  fermentation  the  reducing-substance 
has  disappeared  or  diminished,  it  may  be  concluded  that  it  was  glu- 
cose or  levulose  or  maltose,  of  which  saccharids  glucose  is  very 
common  in  urine  and  the  two  others  are  extremely  rare. 

By  omitting  the  fermentation-test  and  by  trusting  only  to  reduction-tests, 
one  incurs  great  danger  of  increasing,  in  his  own  mind  or  in  the  literature,  the 
large  number  of  cases  of  false  glycosurias. 

Referring  for  further  particulars  to  the  special  manuals,  I  would  here  only 

*  Worm-Miiller  found  that  though  the  sugar  reduces  more  readily  at  a  higher  temper- 
ature than  70°  or  75°  C.  (158°  or  167°  F.),  a  reduction  at  this  higher  temperature  is 
easily  brought  about  by  other  substances  than  glucose.  At  a  lower  temperature  than  70° 
C.  (158°  F.)  the  test  is  less  delicate. 

The  decoloration  of  the  urine,  which  was  first  practised  by  Claude  Bernard,  was 
adopted  by  Seegen  as  a  modification  of  Trommer's  test,  for  the  purpose  of  eliminating 
the  reducing  uric  acid  and  substances  that  prevent  the  cupric  oxid  from  being  precipitated. 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  239 

recapitulate  that  glucose  reduces  Fehling's,  Nylander's,  and  Barfoed's*  solu- 
tions, turns  the  ray  of  polarized  light  to  the  right,  and  is  readily  and  completely 
decomposed  into  alcohol,  carbonic  acid,  etc.,  by  the  influence  of  common  yeast 
and  of  saccharomyces  apiculatus.  Its  crystals  of  osazone  melt  at  205°  C. 
(401°  F.). 

Uric  acid  and  kreatinin,  which  are  present  normally  and  constantly  in  the 
urine,  cause  reduction,  but  do  not  undergo  fermentation. 

Many  of  the  combined  glycuronic  acids,  some  of  which  are  present  in 
normal  urine  (in  combination  with  indoxyl,  skatoxyl,  phenol,  etc.),  also 
cause  reduction.  After  the  ingestion  of  chloral  there  may,  with  or  without 
glucose,  be  quite  a  considerable  reduction  from  the  presence  of  urochloral 
acid  (=  trichlorethyl-glycuronic  acid).  The  combined  glycuronic  acids  do  not 
undergo  fermentation,  and  turn  the  ray  of  polarized  light  to  the  left.j  One 
may  remove  the  combined  glycuronic  acids  from  the  urine  with  ammonia  and 
lead-acetate. 

Many  substances  besides  may  be  responsible  for  the  presence  in  the  urine 
of  nonsaccharine  reducing-substances,  some  of  which  probably  are  combined 
glycuronic  acids.  Other  substances,  such  as  benzoic,  salicylic,  oxalic,  prussic, 
and  mineral  acids,  turpentine,  different  phenols,  morphium,  copaiba,  glycerin, 
kairin,  sulphonal,  trional,  arsenic,  caustic  alkali,  etc.,  may  cause  true  glyco- 
suria. Rhubarb,  senna,  eucalyptus,  large  doses  of  quinin,  also  cause  a  reaction 
with  Nylander's  solution  similar  to  that  caused  by  glucose. 

Alkapton  reduces  Fehling's  solution,  but  not  the  solution  of  bismuth.  It 
does  not  deflect  the  ray  of  polarized  light,  and  it  does  not  undergo  fermenta- 
tion. Urine  containing  alkapton  presents,  after  some  time,  a  brown,  almost  a 
black,  color. 

The  disaccharid  maltose,  which  probably  sometimes  occurs  in  urine,  is, 
like  glucose,  attacked  by  common  yeast ;  but  it  reduces  Fehling's  solution  only 
two-thirds  as  much  as  glucose,  and  it  turns  the  polarized  light  three  times  as 
much  to  the  right.  Unlike  glucose,  maltose  does  not  reduce  Barfoed's  solution, 
which  is,  however,  reduced  to  some  extent  by  other  substances  present  in  all 
urine. 

Levulose  causes  about  as  much  reduction  as  glucose,  and  is  quite  readily 
attacked  by  common  yeast ;  but  it  turns  the  ray  of  polarized  light  to  the  left,  and 
its  osazone  melts  at  190°  C.  (374°  F.). 

Lactose  turns  the  ray  of  polarized  light  to  the  right  and  reduces  Nylander's 
and  Fehling's  solutions.  It  does  not  reduce  Barfoed's  solution,  which, 
unfortunately,  with  regard  to  urine,  does  not  help  us  much,  as  other  sub- 
stances (than  saccharids),  that  are  constantly  present  in  urine,  cause  its  reduc- 
tion ;  but  lactose,  though  it  undergoes  lactic-acid  fermentation  or  alcoholic 
fermentation  with  other  fungi,  does  not  ferment  at  all  with  saccharomyces 
apiculatus,  and  ferments  with  common  yeast  only  when  it  has  been  inverted 
into  its  two  monosaccharids,   glucose  and   galactose,    which   both    ferment. 

*  Barfoed's  solution  is  a  solution  of  from  0.5  to  4  per  cent,  copper-acetate  with  one 
per  cent,  of  free  acetic  acid.     It  is  not  reduced  by  lactose  or  maltose. 

f  Glycuronic  acid/^r  se  turns  the  ray  to  the  right,  but  it  is  never  present  in  urine. 


240  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  inversion  is  likely  to  take  place  spontaneously  after  some  time.  Lactosa- 
zone  melts  at  200°  C.  (392°  F.). 

Galactose  is  not  under  ordinary  circumstances  to  be  expected  in  urine,  but 
may  be  present  after  the  ingestion  of  large  amounts  of  galactose,  and  arises 
(with  glucose)  when  lactose  is  boiled  with  diluted  mineral  acids.  It  reduces 
somewhat  less,  but  turns  the  ray  of  polarized  light  more  strongly  to  the  right 
than  glucose.  Its  osazone  melts  at  193°  C.  (379°  F.).  Laios  (found  by  Leo  in 
1887)  reduces,  but  does  not  ferment. 

Pentoses  reduce,  but  do  not  deflect  the  ray  of  polarized  light  and  do  not  fer- 
ment.    They  are  found  both  in  diabetic  and  in  normal  urine. 

The  substance  found  in  urine  after  the  ingestion  of  turpentine  reduces  and 
ferments,  but  it  does  not  deflect  the  ray  of  polarized  light  (Vetlesen). 

Animal  gum  turns  the  ray  of  polarized  light  to  the  right,  but  does  not  fer- 
ment. It  forms  a  compound  with  the  copper  of  Fehling's  solution,  which  is  pre- 
cipitated in  whitish-blue  flakes. 

If  after  a  generous  mixed  meal  the  urine  contains  no  glucose  as 
determined  by  the  tests  named,  a  distinctly  pathologic  deficiency  in 
the  power  of  assimilation  is  excluded. 

Some  who  have  occupied  themselves  a  good  deal  with  similar  researches 
may  feel  some  doubt  as  to  the  correctness  of  this  assertion.  May  not, 
they  will  probably  urge,  a  simple  glycosuria,  or  even  a  "periodic"  or  an 
"  alternating"  diabetes,  or  a  very  mild  common  diabetes  after  abstinence  from 
carbohydrates  continued  for  some  time,fwithstand  such  a  trial  without  the  ap- 
pearance of  glucose  in  the  urine  ?  To  this  I  would  answer  that  even  in  such 
cases  the  urine  will,  an  hour  after  a  generous  mixed  meal,  yield  to  the  tests 
named  evidence  of  the  presence  of  at  least  a  trace  of  glucose.  I  have  found 
this  to  be  the  case  even  in  individuals  who  have  been  capable  of  taking  large 
portions  of  rice  or  cane-sugar  without  the  development  of  glycosuria.  Escape 
from  detection  in  any  stage  of  the  glycosuric  dystrophy  under  the  circumstances 
named  will  at  all  events  be  exceedingly  rare. 

If  after  a  generous  mixed  meal  the  urine  contains  a  considerable 
quantity  (several  per  cent.)  of  sugar,  the  secretion  is  undoubtedly 
that  of  a  diabetic  individual. 

My  next  step — never  to  be  omitted — will  then  be  to  submit  the 
urine  to  Gerhardt's  test  for  diacetic  acid.  This  is  done  in  a  moment. 
I  almost  fill  an  ordinary  test-tube  with  urine  and  add  six  or  eight 
drops  of  a  solution  of  ferric  chlorid.  If  the  urine,  with  the  patient 
in  his  customary  state  and  with  a  good  supply  of  calories  in  his  food, 
turns  a  red,  or,  still  more,  if  it  turns  a  dark  bluish-red  color,  the 
patient  is,  without  doubt,  in  the  severe  stage  of  diabetes.  It  is  then 
unnecessary,  and,  besides,  it  would  incur  danger  of  coma,  to  exclude 
carbohydrates  from  the  patient's  food. 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  24 1 

If  Gerhardt's  reaction  is  wanting  or  indistinct,  I  may,  without 
danger,  so  far  as  possible  exclude  carbohydrates  from  the  diet  for 
several  days  or  a  couple  of  weeks.  If  during  this  regime  the  urine 
becomes  free  from  glucose,  the  patient  is  in  the  mild  stage  ;  but  if 
sugar  appears,  he  has  entered  upon  the  severe  stage  of  diabetes. 

Having  ascertained  that  the  patient  is  in  the  mild  stage  of  dia- 
betes, it  must  be  determined  how  much  carbohydrate  he  is  capable 
of  taking  without  the  development  of  glycosuria.  For  practical 
purposes  this  is  best  done  by  allowing  the  patient,  in  addition  to 
generous  animal  food,  a  certain  amount  of  the  kind  of  bread  that  he 
prefers.  In  doing  this  I  may  either,  after  absolute  exclusion  of 
bread,  permit  larger  and  larger  amounts  until  glycosuria  appears, 
or  diminish  the  amount  after  a  more  generous  supply  until  the  gly- 
cosuria ceases  ;  and  it  is  not  an  entirely  indifferent  matter  which  of 
these  plans  I  select.  With  exclusion  of  carbohydrates  or  restriction 
of  them  below  his  power  of  assimilation  the  patient  increases  this 
power,  and  thus,  by  progressing  from  small  to  larger  amounts,  I  may 
find  a  higher  power  of  assimilation  than  by  pursuing  the  opposite 
course.  If  I  am  anxious  in  a  case  not  to  give  the  patient  more  car- 
bohydrates than  he  can  take  continually  without  the  development 
of  glycosuria,  I  proceed  from  amounts  of  carbohydrate  that  are 
beyond  his  power  of  assimilation,  and  decrease  them  until  glyco- 
suria disappears.  In  either  event  I  use  for  analytical  purposes 
samples  from  the  whole  amount  of  urine  collected  during  twenty- 
four  hours. 

If  after  a  generous  mixed  meal  I  find  only  a  small  quantity  of 
glucose  in  the  urine,  I  must  submit  the  case  to  further  investiga- 
tion before  giving  the  dystrophy  a  name  or  forming  a  concrete 
opinion  as  to  its  nature.  In  this  case,  too,  I  always  take  for 
analysis  a  sample  of  the  urine  collected  and  measured  during 
twenty-four  hours,  while  the  patient  consumes  with  his  daily  food 
a  rather  large,  determined  amount  of  carbohydrates,  represented  by 
from  150  to  200  grams  of  bread  and  some  potatoes,  rice,  macaroni, 
peas,  and  cane-sugar.  The  patient  should  observe  this  regime  for 
a  few  days  before  collecting  his  urine  for  the  test.  If  under  such 
circumstances,  and  with  the  patient  in  his  habitual  state,  tlie  mixed 
wdne  for  twenty-four  hours  contains  a  determinable  amount  of  glu- 
cose, amounting  at  least  to  several  tenths  of  a  per  cent.,  the  case  is 


242  DIABETES    MELLITUS    AND    GLYCOSURIA. 

one  of  true,  though  it  may  be  very  mild,  diabetes,  and  I  am  then 
generally  able  to  find  other  purely  diabetic  symptoms  besides 
glycosuria. 

If  an  individual  excretes  for  a  short  time  after  every  generous 
mixed  meal  a  determinable  quantity  of  glucose,  which  in  the  urine 
passed  at  that  time  may  occasionally  reach  perhaps  even  one  per 
cent,  or  somewhat  more,  but  which,  in  the  whole  amount  of  urine  for 
the  twenty-four  hours,  during  a  continued,  abundant  supply  of  carbo- 
hydrates, is  present  in  scarcely  more  than  traces,  or,  at  all  events,  in 
less  than  several  tenths  of  a  per  cent.,  the  decision  as  to  whether 
the  case  shall  be  called  one  of  simple  glycosuria  or  of  light  dia- 
betes is  to  a  certain  extent  a  matter  of  opinion. 

Still,  continued  investigation  will  elicit  further  information  as  to 
the  patient's  state  and  future  prospects. 

The  patient,  therefore,  may  be  given,  one  morning  for  breakfast, 
exclusively,  a  large  portion — e.  g.,  200  grams — of  dry  rice,  well 
cooked  in  milk  or  water.  The  urine  is  then  collected  for  six  or 
eight  hours.  Even  in  cases  in  which,  after  every  generous  mixed 
meal,  glycosuria  appears,  the  urine,  after  such  an  amount  of  rice, 
may  remain  perfectly  free  from  glucose.  I  am  then  inclined  to  call 
the  case  one  of  simple  glycosuria,  which,  especially  in  middle  or 
advanced  age,  generally  is  of  no  noteworthy  clinical  importance. 
A  recurring  glycosuria  after  meals  consisting  exclusively  of  rice  or 
bread,  has,  on  the  other  hand,  a  deeper  significance  than  the  same 
phenomenon  after  generous  mixed  meals  or  after  the  ingestion  of 
large  amounts  of  cane-sugar,  and  I  consider  the  designation  diabe- 
tes in  such  a  case  better  to  represent  the  clinical  condition  and  the 
prognostic  aspect  than  that  of  simple  glycosuria. 

If  after  the  ingestion  of  large  quantities  of  rice  the  patient  exhibits 
no  glycosuria,  I  give  him  on  another  day  200  or  300  grams  of  cane- 
sugar,  which  is  most  easily  taken  dissolved  in  some  mineral  water 
containing  free  carbonic  acid.  An  individual  who,  after  the  ingestion 
of  large  amounts  of  boiled  rice,  excretes  glucose  with  his  urine  will 
also  do  so  after  the  ingestion  of  large  amounts  of  cane-sugar.  It  is 
quite  possible,  however,  that  a  person  in  whom,  after  every  dinner 
of  mixed  food,  glycosuria  appears  may  exhibit  none  after  the  in- 
gestion of  large  amounts  of  cane-sugar,  but  only  excrete  some  un- 
changed saccharose,  as   everybody  without  exception  does   under 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  243 

the  circumstances.  In  such  a  case  the  urine  will  not  reduce  Feh- 
ling's  and  Nylander's  solutions  before  but  only  after  being  boiled 
with  several  drops  of  sulphuric  acid.  I  then  call  the  case  one  of 
simple  glycosuria.  In  other  cases  the  ingestion  of  a  Hke  amount  of 
cane-sugar  will  be  followed  by  the  appearance  in  the  urine  of  a  mix- 
ture of  cane-sugar  and  glucose,  and  I  find  more  marked  reduction 
after  boiling  with  sulphuric  acid  than  before,  the  difference  rep- 
resenting the  amount  of  cane-sugar  that  had  passed  through  the 
organism  unchanged.*  Such  a  case  always  represents  a  weakened 
power  of  assimilation,  and  is  either  one  of  simple  glycosuria  or  of 
diabetes.  Referring  to  chapter  11  of  this  book,  I  am  the  more  in- 
clined to  the  milder  name  and  the  more  favorable  prognosis,  the 
more  unchanged  cane-sugar  and  the  less  glucose  the  patient  ex- 
cretes. 

It  is  also  possible  to  test  the  power  of  assimilation  by  the  administration  of 
a  large  amount  of  glucose  ;  only  as  all  persons  excrete  glucose  after  the  inges- 
tion of  very  large  amounts  of  this  saccharid,  the  necessary  quantity  of  which 
varies  greatly  even  in  the  same  individual  under  apparently  similar  conditions, 
and  as  under  ordinary  conditions  such  amounts  of  glucose  are  never  taken,  I 
prefer  the  other  tests.  From  my  own  researches  I  will  say  that  the  develop- 
ment of  glycosuria  after  the  ingestion  of  100  grams  of  glucose  often  denotes  a 
weakened  power  of  assimilation.  In  using  ordinary  "technical"  glucose, 
mixed  with  dextrin,  one  ought  to  put  the  test-amount  at  least  at  150  grams. 
Achard  and  Weil  (1898)  inject  10  cu.  cm.  of  pure  glucose  subcutaneous ly,  and 
consider  the  appearance  of  glycosuria  after  this  pathologic.  In  a  normal 
person,  whose  bodily  weight  unfortunately  is  not  mentioned,  Fritz  Voit  found 
(1896),  after  the  subcutaneous  injection  of  sixty  grams  of  glucose,  a  trace  of 
sugar  in  the  urine  ;  100  grams  given  in  the  same  manner  caused  a  glycosuria  of 
2.6  grams.  (Biedl,  R.  Kraus,  and  Pavy  have  made  similar  researches.  If  made 
in  large  numbers  under  different  dietetic  conditions,  and  with  a  determination  of 
the  bodily  weight,  experiments  with  subcutaneous  injections  may  provide  the 
means  of  finding  some  exact  expression  for  the  normal  power  of  assimilation.) 
To  decide  immediately  and  after  a  single  investigation  the  nature  and  the 
prognosis  of  a  slight  excretion  of  sugar,  is,  as  may  be  understood  from  the 
foregoing,  quite  impossible.  Neither  does  there  at  present  exist  any  universal 
rule  for  the  refusal  or  acceptance  of  an  application  for  life-insurance  in  these 

*  By  boiling  with  diluted  sulphuric  acid  the  cane-sugar  is  "  inverted  "  into  a  mixture  of 
glucose  and  levulose.  The  former  turning  the  ray  of  polarized  light  to  the  right,  the 
latter  to  the  left,  polarization  yields  no  information.  Both  saccharids,  however,  cause 
practically  equal  reduction  (levulose  /^%%  as  much  as  glucose),  and  titration  before  and 
after  boiling  yields  information  as  to  the  amount  of  glucose  and  the  amount  of  cane- 
sugar  excreted. 


244  DIABETES    MELLITUS    AND    GLYCOSURIA. 

cases,  and  the  physicians  of  insurance  companies  often  decide  the  fate  of  such 
applications  in  a  most  summary  way.  Some  examiners  perform  the  analysis 
in  tlie  morning,  when  the  patient's  stomach  contains  no  food,  or  without  any 
information  as  to  his  diet.  In  this  way  many  a  diabetic  in  the  mild  stage 
secures  life-insurance.  On  other  occasions  applications  are  refused  on  account 
of  a  slight  and  accidental  excretion  of  sugar.  The  most  rational  manner  of 
reaching  a  decision  from  a  single  investigation  is,  perhaps,  to  have  the  appli- 
cant partake  of  a  large  amount  of  rice  with  cane-sugar,  and  two  hours  afterward 
pass  his  urine  for  analysis.  If  such  a  specimen  yields  no  distinct  reaction  for 
sugar,  there  is  no  reason,  on  a  diabetic  basis,  for  refusing  the  insurance ;  if  the 
urine  contains  a  slight  amount  of  glucose,  the  insurance  ought  to  be  refused 
until  more  careful  investigation  shall  settle  the  question  as  between  simple 
glycosuria  or  mild  diabetes,  when  insurance  should  be  refused  in  the  latter  and 
accorded  on  higher  premiums  in  the  former  case.  Even  with  this  test  many 
persons  who  habitually  excrete  sugar  after  mixed  meals  would  be  accepted  as 
first-class  risks,  and  the  same  might  happen  in  rare  instances  of  true  diabetes 
after  prolonged  abstinence  from  carbohydrates.  It  is  perhaps  possible  to 
decide  diagnostic  questions  quickly  by  Bremer's  new  tests,  which  are  described 
immediately  below,  but  which  I  have  not  yet  had  time  to  study. 

Dr.  Lud wig  Bremer,*  of  St.  Louis,  has  made  the  interesting  and 
important  discovery  that  diabetic  blood  (to  the  naked  eye)  and  its 
red  blood-corpuscles  (microscopically)  are  colored  differently  from 
normal  blood  by  certain  dyes,  whether  there  is  or  is  not  for  the 
moment  sufficient  hyperglycemia  to  induce  glycosuria.  It  is  as  yet 
not  known  at  what  stage  in  the  development  of  glycosuric  dystro- 
phy this  peculiarity  of  the  blood  first  appears,  but  some  of  Bremer's 
cases  were  instances  of  glycosuria  (according  to  his  views  f),  and  it 
seems  that  we  have  in  this  method  a  means  also  of  detecting  the 
glycosuric  dystrophy  in  its  incipiency. 

Equal  parts  of  saturated  watery  solutions  of  methylene-blue  and 
eosin  are  mixed,  and  the  precipitate  that  forms,  and  which  is  insoluble 

*"  New  York  Med.  Jour.,"  1896. 

f  Dr.  Bremer's  views  on  other  subjects  differ  widely  from  my  own  and  from  those 
held  by  most  students  of  diabetes.  When  Dr.  Bremer  says  :  "  It  is  a  well-known  fact 
that  by  means  of  dieting,  and  by  the  administratiott  of  certain  drugs  (antipyrin,  calo- 
mel, and  ammonium  carbonate),  the  sugar  can  be  made  to  temporarily  greatly  diminish 
or  entirely  disappear  from  the  urine,  even  in  cases  of  well-established  and  undoubted 
diabetes,"  or  that  "  fasting  is  a  tolerably  certain  means  of  freeing  the  urine  from 
sugar,"  I  can  scarcely  approve  of  his  expressions,  nor  do  I  share  his  opinions.  I  do 
admit,  however,  tliat  Dr.  Bremer  deserves  great  credit  for  his  important  discovery,  which 
in  some  cases  probably  will  constitute  a  valuable  diagnostic  means,  and  which  may  lead 
to  a  better  knowledge  of  the  diabetic  changes  in  the  red  blood-corpuscles. 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  245 

in  water,  but  soluble  in  alcohol,  is  washed  and  dried  on  a  filter.  To 
this  powder  some  methylene-blue  (usually  about  one-sixth  by  weight) 
and  some  eosin  (about  one  twenty-fourth  by  weight)  are  added. 
The  whole  forms  a  powder  of  reddish-brown  color.  Every  time  the 
test  is  to  be  made  a  fresh  test-solution  is  to  be  prepared  by  dissolv- 
ing from  0.025  to  0.05  gram  of  this  powder  in  about  10  grams  of 
dilute  alcohol  (1:3).  A  drop  of  blood  from  the  finger  of  the 
patient  is  spread  between  two  cover-glasses,  which  are  then  boiled 
over  a  water-bath  for  four  minutes  in  equal  parts  of  alcohol  and 
ether,  to  fix  the  hemoglobin  in  the  red  blood-corpuscles,  and  trans- 
ferred to  the  staining  solution  described  for  about  the  same  length 
of  time.  After  washing  the  cover-glasses  in  water,  normal  blood 
appears  reddish-violet,  while  glycosuric  or  diabetic  blood  presents 
a  sap-green  or  sometimes  a  bluish-green  color. 

In  a  later  notice  *  Dr.  Bremer  has  adopted  a  simpler  method, 
spreading  a  drop  of  blood  between  the  cover-glasses  and  exposing 
these  for  from  six  to  ten  minutes  at  a  temperature  of  135°  C. 
(275°  F.) — not  below  129°  C.  (264.2°  F.)  nor  above  140°  C.  (284° 
F.).  The  cover-slips  are  then  placed  for  several  minutes  in  a 
one  per  cent,  solution  of  Congo-red  or  of  methylene-blue,  or 
Biebrich's  or  Ehrlich-Biondi's  stain.  The  Congo-red  colors  dia- 
betic blood  but  faintly  or  not  at  all,  while  it  gives  normal  blood 
a  bright  red  hue.  Methylene-blue,  which  gives  normal  blood  a 
violet  color,  gives  diabetic  blood  a  faint  greenish  or  yellowish- 
green  color.  Biebrich's  stain  does  not  color  normal  blood,  but 
makes  diabetic  blood  a  purple-red.  Ehrlich-Biondi's  stain  makes 
diabetic  blood  orange  and  normal  blood  violet. 

Dr.  Williamson,  of  Manchester,  with  a  capillary  tube  mixes 
twenty  volumes  of  blood  with  forty  volumes  of  water,  forty  vol- 
umes of  a  six  per  cent,  solution  of  potassium  hydrate,  and  one  vol- 
ume of  a  solution  of  methylene-blue  (i  :  6000),  and  keeps  the  whole 
in  boiling  water  for  five  minutes.  In  the  presence  of  normal  blood 
the  mixture  remains  blue  and  afterward  becomes  greenish,  while 
with  diabetic  blood  the  mixture  turns  a  pale  yellow. 

Loewy  and  others  found  Bremer's  and  Williamson's  tests  valuable 
even  when  the  diabetic  patient's  urine  did  not  contain  glucose. 

*"  New  York  Med.  Jour.,"  1897. 


246  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Patients,  however,  submit  much  more  readily  to  examination  of 
their  urine  than  to  examination  of  their  blood,  and  these  tests  are 
little  Hkely  ever  to  come  into  general  practice.  It  is,  therefore,  of 
great  importance  that  Dr.  Bremer  (1897)  has  published  a  method  of 
performing  a  color-test  zvith  the  tirine.  A  small  quantity  of  a  powder 
consisting  of  three  parts  of  gentian-violet  and  two  parts  of  eosin  is 
introduced  into  a  tube  almost  filled  with  urine.  Even  at  ordinary 
temperature,  but  more  quickly  on  application  of  heat,  diabetic 
urine  assumes  a  deep  violet,  almost  blue  color ;  normal  urine,  a 
brownish-red  color.  This  reaction,  which  appears  whether  the 
diabetic  urine  contains  glucose  or  not,  is  explained  by  the  solution 
of  gentian-violet  in  diabetic  but  not  in  normal  urine.  In  persons 
with  simple  glycosuria,  but  living  on  the  boundary-line  of  diabetes, 
the  urine  presents  a  combination  of  the  two  colors. 

I  believe  that  these  most  interesting  tests  will,  in  combination 
with  those  hitherto  employed,  prove  most  valuable  in  cases  of 
life-insurance  and  in  cases  of  simulated  diabetes  (see  below),  and 
I  intend,  as  soon  as  time  permits,  to  devote  a  good  deal  of  attention 
to  Bremer's  tests. 

A  medical  practitioner's  knowledge  of  a  diabetic  patient's  urine 
must  comprehend : 

1.  The  quantity 

2.  The  specific  gravity 

3.  The  quantity  of  glucose  )   of  the  urine  collected  during  twenty-four  hours, 
upon  a  determined  sup- 
ply of  carbohydrates 

4.  The  absence  or  presence  of  Gerhardt's  reaction  and,  if  possible,  of  /8-oxybutyric 
acid. 

5.  The  absence  or  presence  of  albumin  and  of — 

6.  Structural  elements  from  the  kidneys. 

To  obtain  information  with  regard  to  the  excretion  of  urine  for  the  twenty- 
four  hours,  it  is  necessary  expressly  and  most  distinctly  to  instruct  the  patient 
that  he  must  collect  every  drop  of  urine  in  one  vessel  from,  e.  g.,  8  o'clock  one 
morning  until  8  o'clock  the  next  morning.  Any  one  but  a  physician  would 
believe  this  task,  or  at  least  the  full  understanding  of  it,  to  be  the  easiest  possi- 
ble. In  this,  however,  as  in  everything  else,  we  often  find  painful  illustrations 
of  the  correctness  of  Billroth's  appropriate  remark  :  In  matters  pertaining  to 
the  natural  sciences  the  average  man  is  quite  stupid  ("  ganz  dumm  "). 

To  take  the  specific  gravity  one  must  have  at  least  two  urometers,  one 
graduated  from  i.ooo  to  1.020,  and  another  from  1.020  to  1.040.  A  specific 
gravity   above    1.040  is  rare.     The    fourth  decimal  must  generally  be  taken 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  24/ 

without  any  corresponding  gradation  on  the  urometer,  which  rarely  is  graduated 
to  more  than  three  decimals. 

A  practitioner  who  does  not  observe  many  diabetic  patients  generally  pos- 
sesses no  polarimeter,  and  finds  reduction  by  Fehling's  solution  (or  like 
methods)  too  tedious  a  mode  of  determining  the  degree  of  glycosuria.  For 
him  Roberts'  method,  based  upon  the  difference  in  the  specific  gravity  of  the 
urine  before  and  after  complete  fermentation,  is  the  easiest  and  best  for  deter- 
mining the  percentage  of  glucose  present.  A  glass  cylinder  is  almost  filled 
with  urine,  the  specific  gravity  taken  to  four  decimals,  about  two  grams  of 
common  yeast  added,  the  yeast-cells  somewhat  evenly  distributed  through  the 
liquid  by  stirring,  and  the  cylinder,  covered  with  a  piece  of  glass,  placed  for 
fermentation  if  possible  in  a  room  with  a  temperature  somewhat  above  the 
ordinary.*  After  two  or  three  days  it  is  ascertained  with  Nylander's  or  Feh- 
ling's solution  that  no  determinable  amount  of  glucose  remains,  and  the 
specific  gravity  is  again  taken  to  four  decimals.  The  latter  figure  is  subtracted 
from  that  first  obtained,  and  the  difference  is  multiplied  by  a  coefficient,  which 
has  been  differently  estimated  and  varies  somewhat  with  the  percentage  of 
sugar,  but  which  for  practical  purposes  may,  according  to  Lohnstein,  be  put  at 
the  constant  234.  The  results  thus  obtained  scarcely  differ  from  the  correct 
ones  by  as  much  as  o.oi  per  cent.,  and  they  are  sufficiently  accurate  for  the 
purposes  of  the  general  practitioner.     Thus  : 

Specific  gravity  before  fermentation  was  1.0345,  and  the 

"  "       after  "  "     1.0165 ;  the 

Percentage  of  sugar  is  0.0180  X  234  =  4.86. 

Finally,  I  must  again  emphasize  the  necessity  of  performing  Gerhardt's  test, 
the  easiest,  the  most  important,  and  the  most  neglected  of  all.  Into  an  ordinary 
test-tube  nearly  filled  with  urine,  six,  eight,  or  ten  drops  of  a  solution  of  ferric 
chlorid  are  poured ;  a  red  or  a  dark  bluish-red  color  denotes  the  presence 
of  diacetic  acid.  There  is  no  method  of  quickly  ascertaining  the  quantity. 
Oppler,  of  Breslau,  adds  the  solution  of  ferric  chlorid  until  the  maximum  in- 
tensity of  color  is  reached ;  he  then  adds  diluted  hydrochloric  acid  until  the 
color  again  disappears.  From  the  quantity  of  hydrochloric  acid  necessary  for 
this  purpose  an  idea  is  gained  as  to  the  quantity  of  diacetic  acid. 

The  practitioner  who  does  not  use  a  polarizing  instrument  can  not  determine 
the  presence  or  the  quantity  of  /3-oxybutyric  acid,  which  permits  him  to  form  a 
distinct  opinion  with  regard  to  the  danger  of  coma.  There  are  some  points 
apart  from  this  best  mode  of  estimating  such  a  danger  that  it  is  important  to 
observe.  If  the  reaction  with  six  or  eight  or  ten  drops  of  a  solution  of  ferric 
chlorid  in  a  test-tube  almost  filled  with  the  patient's  urine  does  not  yield  a  true 
red,  but  only  a  brownish  color,  there  is  no  considerable  amount  of  /3-oxybutyric 
acid  present  either  in  the  urine  or  in  the  blood.  If  a  distinct,  but  not  pro- 
nounced, Gerhardt's  reaction  with  a  light  red  color  appears,  the  amount  of 

*  The  specific  gravity  of  urine  sinks  about  o.ool  with  every  increase  of  temperature  of 
3°  C.  (5.4°  F.).  To  obviate  the  necessity  of  corrections  and  to  avoid  possible  errors,  it 
is  best  to  determine  the  specific  gravity  in  both  instances  at  the  same  temperature. 


248  DIABETES    MELLITUS    AND    GLYCOSURIA. 

j3-oxybutyric  acid  present  is  not  large,  and,  unless  the  patient's  general  state  is 
very  miserable,  there  will  scarcely  be  any  danger  of  coma.  If  the  solution  of 
ferric  chlorid  yields  a  deep,  dark  bluish-red,  there  is  good  reason  to  suspect  the 
presence  of  a  larger  quantity  of  ,'3-oxybutyric  acid.  The  degree  of  danger  of 
coma  in  such  cases  depends  in  large  part  upon  the  patient's  general  state.  As 
has  been  already  mentioned,  one  patient  may  go  on  for  months  excreting  in 
the  twenty-four  hours  many  times  as  much  /3-oxybutyric  acid  as  is  excreted  by 
another  patient  for  only  a  short  time  before  the  fatal  degree  of  poisoning  is 
reached. 

By  the  use  of  a  polarimeter  the  task  is  much  facilitated.  After  precipitating 
with  ammonia  and  lead-acetate  a  sample  of  the  mixed  urine  collected  during 
twenty-four  hours,  and  waiting  for  some  time  until  the  urine  passes  perfectly 
clear  through  the  filter,  the  number  of  grams  of  the  acid  excreted  in  the  twenty- 
four  hours  is  easily  determined  by  introducing  the  degree  of  levogyration  into 
the  formula,  with  the  necessary  correction  for  the  dilution  of  the  urine.  As 
soon  as  this  number  reaches  more  than  twenty  in  an  adult,  the  "acidosis," 
operating  in  combination  with  a  low  state  of  general  health,  may  threaten 
coma. 

To  demonstrate  the  presence  of  albumin  there  is  no  easier  test  than  pouring 
nitric  acid  into  a  test-tube  with  a  pipet  beneath  the  urine.  Even  when  only  a 
trace  of  albumin  is  present,  it  then  quickly  shows  as  a  thin,  reddish-white  layer 
immediately  above  the  line  of  contact  of  the  two  liquids,  below  the  less  sharply 
defined,  more  grayish  layer  of  urates,  which  often  forms  above  it ;  care  being 
taken  when  only  one  of  the  two  layers  is  present  not  to  mistake  it  for  the  other. 

The  quantity  of  albumin,  which  generally  is  small  and  often  below  one- 
half  in  a  thousand,  is  most  practically  and  enough  accurately  determined  by 
means  of  Esbach's  albuminimeter. 

With  the  aid  of  a  centrifuge  the  task  of  finding  casts  of  the  renal  tubules  is 
much  facilitated,  care  being  taken  not  to  permit  hyaline  casts  to  escape  detection, 
and  in  cases  of  severe  diabetes  to  keep  a  sharp  lookout  for  the  numerous  small 
casts  described  by  Kiilz. 

It  is  often  worth  the  trouble  to  ascertain  the  patient's  capabihty  of  ingesting 
and  digesting  proteids  by  determining — usually  by  Kjeldahl's  method  or  by 
one  of  the  many  azotometers — the  quantity  of  nitrogen  excreted  with  the  urine 
in  twenty-four  hours.  By  multiplying  the  number  of  grams  of  nitrogen  by  6.25 
the  number  of  digested  grams  of  proteids  is  learned,  not  taking  into  considera- 
tion the  nitrogen  possibly  ingested  with  other  substances  than  proteids  and  the 
nitrogen  derived  from  toxic,  protoplasmic  disintegration,  both  of  which,  in  most 
cases,  only  form  "  une  quantite  neglige  able,''  and  can  not  possibly  be  deter- 
mined by  the  physician. 

The  general  practitioner  usually  finding  among  his  patients  but  a 
limited  number  of  diabetics,  as  a  rule  does  not,  by  analytic  work, 
ascertain  the  changes  in  their  nutritive  state.  On  the  other  hand, 
he  ought  not  to  omit  to  follow  these  changes,  even  though  in  a 
somewhat  crude  but  simple  and  practical  manner.      For  this  pur- 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  249 

pose  he  may  use  the  scales,  the  patient  being  weighed  once  a  month, 
or,  if  necessary,  once  a  week.  In  doing  this  the  patient  must 
necessarily  take  his  weight  at  the  same  time  of  day  and  in  the 
same  dress,  or,  if  convenient,  without  any  clothes  at  all.  It  is 
evident  that  even  if  this  is  done  the  varying  contents  of  the  bowels 
and  the  bladder  may  give  rise  to  error.  Further,  a  less  important 
gain  of  fat  may  cover  and  conceal  a  more  important  loss  of  pro- 
teids.  However  crude  this  method  of  following  the  patient's  nutri- 
tive changes,  it  is  of  great  practical  importance,  and,  especially  in 
two  classes  of  cases,  is  not  to  be  neglected  by  the  conscientious 
physician.  In  severe  cases  it  enables  us  to  discover,  and  at  once  by 
all  the  means  in  our  power  to  combat,  any  increase  of  the  autoph- 
agy  and  rapid  loss  of  weight,  which  often  indicate  the  beginning 
of  the  end  and  the  overwhelming  danger  of  coma.  In  mild  cases 
the  scales  enable  us,  during  periods  of  marked  restriction  or  exclu- 
sion of  carbohydrates  from  the  food,  to  control  the  loss  of  weight 
that  usually  occurs  under  such  conditions,  and  which  ought  not  to 
be  too  marked.  A  fat  diabetic  patient  (in  the  mild  stage)  may — 
ceteris  paribus — be  permitted  to  lose  more  than  a  less  fat  patient, 
but  no  diabetic  should  be  permitted  to  lose  in  a  month  more  than  a 
small  percentage  of  his  whole  bodily  weight.  In  the  severe  stage 
the  physician  should  always  do  his  best  to  prevent  any  loss  of 
weight. 

The  remaining  part  of  the  investigation  in  a  case  of  diabetes  occu- 
pies comparatively  little  time.  I  will  cursorily  mention  the  points 
that  strike  me  as  most  important. 

In  examining  the  patient  as  to  his  heredity  one  has  especially  to 
bear  in  mind  diabetes  mellitus  and  insipidus,  gout,  adiposity,  and 
all  neuroses  (various  forms  of  mental  disease,  neurasthenia,  epi- 
lepsy, etc.),  and  exophthalmic  goiter.  In  making  inquiry  as  to 
mental  diseases  one  must  sometimes  press  the  question  in  order 
to  gain  the  necessary  information  ;  an  unintelligent,  and  sometimes 
even  an  intelligent,  patient  may,  however,  be  irritated  if  the  pres- 
sure be  made  too  great.  A  satisfactory  result  is  often  more  easily 
reached  by  asking  as  to  symptoms  rather  than  about  names  of 
diseases. 

With  regard  to  the  patient's  own  life  inquiry  is  made  as  to  past 
diseases,  especially  gout,  influenza,  malaria,   syphilis  ;   trauma,  es- 
17 


250  DIABETES     MELLITUS   AND    GLYCOSURIA, 

pecially  of  the  head  ;  excessive  intellectual  work  ;  powerful  and 
permanent  painful  emotions  ;  sexual  excesses,  natural  or  unnatural ; 
deprivations  ;  exposure  ;  indulgence  in  alcohol,  tobacco,  or  other  in- 
toxicants (morphin,  cocain,  chloral)  ;  gormandism  ;  overindulgence 
in  sweets  ;  sedentary  habits,  etc. 

If  the  diabetes  has  been  discovered  and  treated  before  my  own 
investigation,  I  never  omit  to  ask  whether  the  discovery  was  made 
from  the  sudden  appearance  of  diabetic  symptoms  (thirst,  polyuria, 
etc.)  or  whether  the  disease  has  developed  slowly  and  has  been  dis- 
covered accidentally  (life-insurance,  etc.)  or  in  consequence  of -some 
chronic  diabetic  comphcation  affecting  the  skin,  the  eyes,  the  teeth, 
etc.  The  prognosis,  as  has  already  been  mentioned,  is  far  better 
when  the  development  is  slow  than  when  the  onset  is  sudden. 

I  likewise  endeavor  to  secure  information  as  to  any  loss  of  bodily 
weight,  and  attach  much  greater  significance  to  this  if  it  has  begun 
before  the  diabetes  was  discovered  and  without  any  change  of  die- 
tetic regimen,  than  if  it  began  after  a  restriction  of  carbohydrates, 
which,  if  carried  to  anything  like  an  extreme,  is  likely  to  cause  loss 
of  flesh  in  any  person,  diabetic  or  not. 

I  observe  the  patient's  general  appearance,  complexion,  manner 
of  movdng  and  of  talking.  I  never  omit  to  examine  the  cavity  of 
the  mouth,  which,  from  the  existence  of  alveolar  pyorrhea  and 
decay  or  loss  of  teeth,  may  afford  evidence  of  diabetes  of  long 
standing,  or  from  the  typical,  diabetic  "crocodile"  tongue,  and  a 
strong  smell  of  acetone  on  the  breath  may  show  that  the  disease 
has  entered  upon  the  severe  stage. 

I  first  try  to  form  an  opinion  as  to  the  patient's  mental  state  by 
my  own  observation,  and  afterward,  prudently — i.  e.,  as  kindly,  in- 
terestedly, and  delicately  as  possible — put  direct  questions  about 
central  nervous  symptoms,  especially  depression  and  irritability.  I 
pay  particular  attention  in  my  examination  to  neurasthenic  symp- 
toms, whether  revealed  more  directly  through  the  nervous  system 
or  the  organs  of  perception,  circulation,  digestion,  and  reproduc- 
tion :  Depression  ;  irritability  ;  sleeplessness  ;  loss  of  memory  or  of 
capacity  for  intellectual  work  ;  vertigo,  spontaneous  or  from  a  great 
depth  ;  agoraphobia  (rare) ;  headache  ;  hj'peresthetic,  dysesthetic, 
or  paresthetic  sensations  {casque  nciirastlicniqiie,  plaqtie  sacree,  and 
other  rachialgic  manifestations,  formication,  sense  of  heat  or  of  cold. 


INVESTIGATION    OF    A    CASE    OF    DIABETES.  25 1 

shooting,  "  rheumatoid  "  pains,  neuralgia,  migraine)  ;  neuromuscular 
asthenia ;  cramps  in  the  calves  ;  neurasthenic  asthenopia ;  hyper- 
esthetic,  ocular,  or  auditory  manifestations  ;  changes  in  taste  and 
smell,  etc. ;  pseudoangina  pectoris — increased  frequency  of  pulse  ; 
gastrointestinal  disorders,  with  a  capricious  appetite  ;  nervous  nausea 
or  vomiting ;  eructations,  pains,  flatulence  (exceedingly  common), 
sudden  diarrheas,  etc.  ;  sexual  weakness  and  impotency. 

In  cases  of  long  standing  or  in  cases  complicated  by  gout  I  do 
not  fail  to  look  for  symptoms  of  neuritis,  and  with  a  needle  or  a 
tube  filled  with  hot  water  or  the  esthesimeter  to  test  the  sensibility, 
especially  on  the  lower  parts  of  the  legs,  where  neuritic  symptoms 
are  more  frequent  and  more  intense. 

I  test  the  knee-jerks  (the  prepatellar  reflexes)  a  la  Jendrassik. 
The  patient  reclines  upon  a  chair  with  his  eyes  closed,  his  legs  bent 
at  the  knee-joint  at  an  angle  of  about  i  lo  degrees,  the  feet  some- 
what separated,  and  the  whole  sole  on  the  floor.  His  hands  are 
joined  over  his  stomach,  and  he  is  told  to  relax  the  whole  muscular 
system,  especially  the  muscles  of  the  legs,  as  much  as  possible.  I 
place  one  hand  near  the  knee,  over  the  quadriceps  femoris  muscle, 
to  feel  the  jerk,  while  with  a  small  book  in  the  other  I  try  to  elicit 
the  reflex  by  striking  a  blow  over  the  ligamentum  patellae.  I  am 
thus  able  to  perceive  by  touch  better  than  by  sight  the  slightest 
contraction  of  the  quadriceps  femoris. 

By  physical  investigation  in  the  usual  way  I  ascertain  the  size 
and  the  functional  and  valvular  state  of  the  heart,  and  I  do  not 
omit  in  forming  an  opinion  as  to  this  state  to  weigh  the  patient's 
statement  with  regard  to  his  capacity  for  climbing,  or  any  other 
energetic  muscular  activity  which  increases  the  demands  on  the 
heart.  Palpation  of  the  radial  artery  discloses  the  frequency, 
rhythm,  and  strength  of  the  pulse  ;  I  try  to  detect  any  possible 
atheromatous  rigidity  of  the  radial,  femoral,  and  temporal  arteries. 

In  examining  the  lungs  I  direct  attention  especially  to  ascertain- 
ing the  absence  or  presence  of  any  incipient  or  advanced  changes  in 
the  upper  lobes. 

I  ask  the  patient  about  his  appetite,  the  regularity  of  his  bowels, 
etc.  If  there  is  any  reason  for  presuming  pancreatic  disease,  I 
request  him  to  observe  if  the  character  of  the  stools  indicates  the 
presence  of  greater  quantities  of  indigested  fat  than  normal,  and  if 


252  DIABETES    MELLITUS    AND    GLYCOSURIA. 

this  is  the  case,  I  give  my  own  special  attention  to  the  subject.  I 
determine  the  size,  the  consistency,  and  the  sensitiveness  of  the 
Hver.  In  deciding  as  to  the  existence  of  incipient  cirrhosis  of  the 
liver  I  attach  great  importance  to  any  enlargement  of  the  spleen, 
and  sacrifice'  some  time  in  carefully  ascertaining  the  size  of  this 
organ.  I  seek  information  with  regard  to  the  presence  of  any 
symptoms  of  gall-stones,  which  are  not  rare  in  cases  of  diabetes. 

I  also  inquire  whether  the  patient  has  been  troubled  by  pruritus 
or  any  local  changes  in  the  genitals. 

I  direct  special  attention  to  the  eyes  and  look  chiefly  for  cataract, 
myopia,  premature  presbyopia,  retinitis,  and  inflammation  of  the 
optic  nerve. 

Simulation  of  diabetes  is  not  rare  in  some  European  countries,  and  is 
generally  attempted  by  persons  who  wish  to  secure  exemption  from  military 
duty. 

To  contrive  the  fraud,  the  simulator  either  (i)  eats  a  large  quantity  of  glucose, 
usually  in  honey,  or  (2)  introduces  some  saccharid  in  his  urine  within  or  with- 
out the  bladder,  or  (3)  takes  a  dose  of  phloridzin  or  of  phloretin. 

The  ingestion  of  a  large  quantity  of  glucose  is  the  shrewdest  method.  The 
consequent  glycosuria,  however,  lasts  only  for  a  few  hours,  and  then  ceases 
when  the  supply  is  cut  off.  It  is  usually  on  the  increase  only  for  about  an  hour, 
and  after  this  time  the  fraud  can  be  discovered  by  giving  a  large  portion  of 
bread,  and  by  observing  that  an  hour  later  the  glycosuria  is  on  the  wane  instead 
of  increasing. 

Fraud  has  sometimes  been  attempted  by  injecting  a  solution  of  some 
saccharid  into  the  bladder  or  by  adding  some  saccharid  to  the  urine  outside 
the  bladder.  (See  the  case  of  Abeles  and  Hoffmann.*)  In  the  latter  case  the 
fraud  is  detected  by  letting  the  simulator  pass  his  urine  under  observation,  or 
by  withdrawing  it  directly  from  the  bladder.  In  both  cases  detection  is  gener- 
ally made  easy  by  the  simulator's  ignorance  of  the  different  kinds  of  saccharids. 
Women  scarcely  ever  know  of  any  other  sugar  than  the  cane-sugar  used  in 
their  household.  Urine  containing  cane-sugar  will  not  reduce  Fehling's  or 
Nylander's  solutions  before  boiling  with  a  dilute  mineral  acid,  but  will  do  so 
after  this,  and  will  turn  the  ray  of  polarized  light  to  the  right.  The  cane-sugar  is 
generally  added  to  the  urine  in  amounts  large  enough  to  give  it  an  exceedingly 
high  specific  gravity,  which  will  immediately  turn  the  physician's  mind  in  the 
right  direction.  If  the  simulator  has  some  knowledge  of  saccharids,  the  situa- 
tion may  be  rendered  more  complicated.  He  may  then  contrive  to  get  some 
really  diabetic  urine  and  inject  it  into  his  bladder  ;  such  a  mode  of  simulation 
can  only  be  detected  by  keeping  the  simulator  under  observation,  or  by  sub- 
jecting his  blood  to  Bremer's  test.     He  is  more  likely,  however,  to  use  the  glu- 

*  *'  Wiener  med.  Presse,"  1876. 


TREATMENT.  253 

cose  sold  for  technical  purposes.  This  contains  a  good  deal  of  dextrin  which 
is  strongly  dextrogyrate,  but  does  not  reduce  solutions  of  copper  nor  bismuth, 
and  the  fraud  is  detected  by  the  polarimeter  indicating  a  much  higher  percent- 
age of  glucose  than  do  reduction-methods  of  estimation. 

If  simulation  by  means  of  phloridzin  or  phloretin  is  suspected,  the  urine 
should  be  tested  with  ferric  chlorid  for  the  brownish-violet  color  yielded  by 
those  substances — it  being  always  borne  in  mind  that  a  somewhat  similar,  but 
more  reddish,  color  is  caused  (i)  by  diacetic  acid  in  cases  of  severe  diabetes,  or 
when  starvation  is  taking  place,  and  (2)  in  any  state  of  health  by  antipyrin, 
salicylic  acid  and  its  salts,  kairin,  thallin,  chinanisol,  and  other  substances. 
By  cutting  off  the  supply  of  phloridzin  or  phloretin  for  fully  three  days  the 
glycosuria  due  to  these  poisons  can  be  stopped. 

If  one  is  provided  with  the  proper  stains  he  will  probably  find  in  Bremer's 
method  of  diagnosticating  diabetes  (see  above)  an  excellent  means  of  detect- 
ing at  once  any  simulation  of  diabetes  in  whatever  manner  it  is  attempted. 


CHAPTER  IX.— TREATMENT. 

Some  prophylactic  measures  may  be  taken  against  diabetes  ;  this 
apphes  especially  to  members  of  families  with  a  neuropathic,  a 
gouty,  or  directly  diabetic  hereditary  predisposition. 

These  measures  are,  in  large  part,  exactly  those  that  are 
rational  in  cases  of  nervous  disposition.  Children  that  begin  life 
thus  handicapped  ought,  still  more  than  others,  to  be  protected 
against  fright  and  other  emotions,  overwork,  and  strains  of  all 
kind,  fatiguing  and  enervating  pleasures  ;  and  they  should  have  all 
of  the  advantages  to  be  derived  from  fresh  air,  bodily  exercise,  baths, 
early  hours,  and  a  systematic  hygienic  life.  It  is  of  paramount 
importance,  after  puberty,  to  guard  such  children  against  an 
abnormal  or  too  early  development  of  sexual  activity.  It  is  also  an 
exceedingly  important  and  fully  rational,  though  often  neglected, 
measure  in  the  choice  of  a  profession  to  direct  such  young  persons 
to  occupations  in  life  that  are  less  likely  than  others  to  develop 
neurotic  tendencies.  In  this  respect  our  descendants  will  certainly 
provide  much  more  carefully  than  we  do  or  even  than  we  now 
would  approve  of  doing. 

It  seems  to  me  that  something  might  also  be  done  in  the  matter 


2  54  DIABETES    MELLITUS    AND    GLYCOSURIA. 

of  diet  to  diminish  an  inherited  danger  of  future  diabetes,  though 
for  my  part  I  consider  this  item  of  diabetic  prophylaxis  to  be  much 
less  efficient  and  important  than  antineurotic  measures.  It  would 
certainly  be  most  unwise  to  diminish  a  child's  supply  of  bread, 
potatoes,  and  other  more  or  less  necessary  articles  of  chiefly  carbo- 
hydrate nature  below  fair  daily  portions  ;  but  nothing  is  lost,  and 
perhaps  something  is  gained,  by  a  rigorous  restriction  of  sweets 
and  sugar  in  the  food  of  such  children.  The  custom  prevalent  in 
some  countries  of  including  beer  and  other  liquors  in  the  dietary 
of  persons  even  below  fifteen  years  of  age  might  also  well  be 
avoided. 

It  not  rarely  happens  that  a  diabetic  patient  asks  his  physician 
with  regard  to  the  advisability  of  marriage,  often,  I  acknowledge, 
with  a  firm,  though  unconscious,  resolution  in  this  respect  not  to 
take  advice  that  is  opposed  to  his  own  inclinations.  If  a  case 
of  true  diabetes  sets  in  before  the  thirty-fifth  or  fortieth  year,  life  will 
generally  be  short.  Impotence  and  sterility  threaten  darkly,  and 
pregnancy  and  maternal  duties  in  woman,  like  sexual  activity  in 
man,  often  favor  the  development  of  the  dystrophy.  The  mortality 
among  children  of  diabetic  parents,  as  has  been  mentioned,  is 
enormously  high,  the  constitutional  inheritance  a  great  handicap 
in  life.  It  would  be  unwise  for  a  physician  to  put  all  these  facts 
distinctly  before  a  patient  who  thinks  of  marrying,  and  who  rarely 
is  to  be  dissuaded  from  doing  so,  but  these  arguments  must  have  a 
profound  influence  on  the  advice  the  physician  will  give.  In  severe 
cases  of  diabetes  there  are  left  but  few  of  the  customary  reasons  for 
marrying. 

The  great  dangers  for  mother  and  child  also  ought  to  be  taken 
into  consideration  in  connection  with  pregnancy  in  diabetic  women, 
and  they  may,  under  certain  circumstances,  justify  artificial  inter- 
ruption of  the  pregnancy.  Such  a  course  in  a  case  of  simple  glyco- 
suria, or  even  in  one  of  true  but  mild  diabetes  in  otherwise  fairly 
good  condition,  might  justly  be  considered  as  malpractice,  and  the 
mere  name  of  diabetes  ought  never  to  be  made  a  safeguard  for  an 
operation  of  this  kind.  I  should  not  hesitate,  however,  to  give  my 
vote  in  favor  of  interrupting  the  pregnancy  in  any  case  of  diabetes 


TREATMENT.  255 

in  the  severe  stage,  or  in  any  case  in  which  the  prospects  of  mother 
or  child  were  gloomy. 

There  is  but  little  to  say  outside  of  general  rules  with  regard  to 
the  hygiene  of  diabetic  patients. 

The  physician  and  his  diabetic  patient  must  never  forget  the 
small  power  of  the  latter  to  resist  deleterious  influences  of  all 
kinds.  Diabetics  are  more  likely  than  others  to  be  affected  by 
emotions  of  a  depressing  nature  and  to  suffer  more  in  consequence. 
Every  physician  who  has  seen  much  of  these  patients  has  learned 
how  especially  careful  one  must  be  not  to  irritate  or  in  any  way  to 
frighten  them,  and  he  will  adopt  the  rule  of  according  to  them,  still 
more  than  to  others,  the  patience  and  forbearance  under  all  cir- 
cumstances— which  is  not  the  lightest  nor  the  least  important  of 
the  many  high  duties  of  the  medical  profession.  The  necessity  of 
avoiding  all  kinds  of  strains  on  his  nervous  system  must  be  earn- 
estly impressed  upon  the  patient.  He  must,  as  far  as  possible, 
limit  his  intellectual  activity  not  only  below  the  level  of  overwork 
for  a  normal  person  but  below  the  level  of  overwork  for  his  own, 
usually  limited,  powers.  He  must  be  most  moderate  in  sexual 
activity.  He  must  forswear  overuse  of  tobacco  and  alcohol, 
and  it  is  still  more  important  for  him  than  for  others  not  to  fall 
into  bad  habits  with  morphin,  cocain,  somniferous  drugs,  etc.  He 
ought  to  take  as  much  exercise  as  he  can  take  without  fatigue. 
He  must  observe  regular  hours,  with  a  large  allowance  of  time 
for  mental  and  bodily  rest.  His  great  sensitiveness  to  exposure, 
and  the  especially  dangerous  consequences  of  cold  make  it  of  par- 
amount importance  for  him  to  be  warmly  dressed,  and  to  wear, 
constantly,  woolen  underclothes.  His  whole  mode  of  life  must  be 
thoroughly  hygienic.  If  he  lives  in  a  rigorous  climate,  it  is  of 
great  advantage  to  him  to  pass  the  coldest  part  of  the  year  in  some 
warmer  place,  observing  there  the  same  scrupulously  hygienic 
regimen  as  at  home. 

The  special  duty  of  taking  into  earnest  consideration  the  diabetic 
patient's  mental  sensitiveness  begins  at  the  moment  the  physician 
discovers  the  existence  of  any  stage  of  the  glycosuric  dystrophy, 
and  concerns  the  statements  to  be  made  to  the  patient  on  this 
subject. 


256  DIABETES    MELLITUS    AND    GLYCOSURIA. 

If  only  a  slight  glycosuria,  but  no  true  diabetes,  is  found,  it  is 
in  many  cases  wise  to  mention  nothing  about  the  matter  to  the 
patient.  Individuals  of  great  sensitiveness,  especially  if  not  highly 
intelligent,  are  often  greatly  affected  by  learning  of  the  excretion 
of  sugar  in  their  urine,  however  slight  and  however  accentuated  by 
the  physician  its  clinical  insignificance.  If  the  urine  for  twenty-four 
hours  does  not  contain  more  than  a  trace  of  glucose  (up  to  0.05 
per  cent.)  with  an  ordinary  free  diet,  and  the  patient  furnishes  any 
ground  for  doubting  his  courage  or  judgment,  other  reasons  than 
the  existence  of  glycosuria  can  always  be  found  for  advising  avoid- 
ance of  the  most  objectionable  kinds  of  food  (sweets,  dry  fruits,  rice, 
macaroni,  peas,  champagne,  etc.). 

If  the  case  is  one  of  true  diabetes,  it  is  generally  necessary  to  in- 
form the  patient  of  this  fact.  In  mild  cases  the  physician  then  has 
the  pleasant  task  of  making  the  patient  acquainted  with  many  actual 
reasons  for  comfort  and  hope.  In  severe  cases  the  physician,  who 
alone  can  determine  the  nature  and  prognosis  of  the  special  case, 
will  understand  that,  if  prudence  often  is  the  better  part  of  valor, 
discretion  is  often  the  better  part  of  truthfulness.  It  is  quite  a 
satisfaction  to  know  that  downright  lying  is  generally  not  necessary. 
The  patient  usually  knows  little  else  of  diabetes  than  that  a  person 
may  live  with  it  for  decades  in  fairly  good  health,  and  the  physician 
will  rather,  by  repeating  this  and  other  general  facts,  let  the  patient 
deceive  himself  than  injure  and  torture  him  by  stating  the  whole 
implacable  truth. 

On  the  whole,  it  is  of  great  importance  to  arrange  everything  for 
the  patient  with  a  view  of  reminding  him  as  little  as  possible  of  his 
own  exceptional  position. 

For  this  reason  I  consider  the  "  sanatoriums  for  diabetics,"  where  the 
patient  meets  only  brothers  in  misfortune,  in  many  cases  to  be  of  doubtful  ad- 
vantage. The  one  indication  that  may  arise  for  a  sojourn  of  some  weeks  in 
such  an  institution  is  the  period  of  absolute  or  of  very  rigid  diet  in  the  mild 
stage ;  it  depends  on  circumstances  whether[the  dietetic  discipline  is  not  even 
then  acquired  at  too  high  a  price. 

The  poor  diabetic  patient  certainly  derives  some  advantage  from  the  hos- 
pital, where  he  may  for  some  time  enjoy  a  rational  diet  at  moderate  cost. 

One  of  the  diabetic's  most  frequent  and  most  common  nervous 
symptoms  is  sleeplessness.     This  is  a  trouble  that  often  follows  the 


TREATMENT.  257 

patient  throughout  his  whole  life,  and  it  is  of  the  utmost  importance 
not  to  employ  remedies  that  easily  lead  the  patient  into  bad  habits 
and  may  cause  a  much  greater  misfortune  even  than  sleeplessness. 
We  therefore,  as  far  as  possible,  take  refuge  in  simple  and  harmless 
remedies.  We  prescribe  mental  and  physical  rest  during  the  last 
hours  of  the  day.  We  recommend  the  system — already  mentioned 
for  its  merits  in  other  respects — of  making  the  last  meal  of  the  day 
a  light  one,  also  for  its  better  influence  on  the  night's  rest.  A 
moderately  warm  bath  at  35°  or  36°  C.  (95°  or  98.6°  F.)  before 
going  to  bed  has  a  good  effect  in  some  cases.  A  hot  foot-bath  at 
this  time  and  a  wet,  warm  fomentation  around  the  abdomen  during 
the  night  are  highly  praised  by  some  patients.  In  other  cases  I 
have  found  covering  the  head  warmly  at  night — with  a  fur  cap,  for 
instance — a  most  efficient  remedy  for  promoting  sleep.  The  vibra- 
tions on  the  head,  recommended  by  Charcot  and  others,  have 
already  been  mentioned.  I  found  Charcot's  (or  Gilles  de  la  Tou- 
rette's)  "  casque  vibrmtt "  too  weak,  and  have  seen  much  better  results 
from  one  of  Zander's  machines.  One  must  sometimes  try  several 
of  these  simple  remedies,  and  will  often  find  one  of  them  efficient 
when  others  have  failed. 

In  the  presence  of  severe  exacerbations  of  insomnia  and  during 
mental  disturbances  we  are  sometimes  forced  to  take  refuge  in 
narcotic,  somniferous  drugs.  I  prefer  great  economy  in  this,  and  I 
rarely  give  such  remedies  two  nights  in  succession  ;  neither  do  I 
us^  them  for  any  length  of  time,  if  this  can  possibly  be  avoided. 
A  large  dose  of  the  comparatively  harmless  bromids  will  diminish 
the  necessary  dose  of  other  remedies.  (I  prefer  sodium  bromid  to 
potassium  bromid.)  Among  directly  hypnotic  remedies,  I  have, 
after  many  disappointments,  returned  to  chloral  hydrate  or  chloral- 
amid  as  the  best  and  least  objectionable.  With  all  their  draw- 
backs, these  are  decidedly  better  than  the  much-praised  sulphonal 
and  trional,  both  of  which  cause  drowsiness  on  the  next  day,  if 
taken  in  such  doses  as  will  cause  sleep  during  the  night,  and 
both  of  which  cut  off  the  systolic  apices  on  the  pulse-curve. 
Among  narcotic  vegetable  derivatives  opium  and  extract  of  can- 
nabis indica  rank  foremost.  Neither  morphin  nor  codein  is 
ever  to  be  used  for  this  purpose.  One  may,  for  instance, 
give     at    one    dose :     sodium    bromid,    2    gm.  ;    chloral     hydrate, 


258  DIABETES    MELLITUS    AND    GLYCOSURIA. 

1.20  gm. ;  extract  of  cannabis  indica,  0.05  gm.  ;  or  some  similar 
formula. 

In  cases  of  severe  diabetes,  with  a  miserable  general  state  and  a 
distinct  excretion  of  /3-oxybutyric  acid,  our  chief  task  must  be  as 
long  as  possible  to  prevent  coma.  The  patient  must  with  the 
greatest  care  be  protected  from  injurious  influences  of  all  kinds. 
No  mental  or  intellectual  exertion,  no  exposure,  no  fatigue,  no 
long  journeys,  no  deviation  from  daily  customs  should  be  per- 
mitted. I  add  with  the  deepest  conviction  that  the  diet  should  not 
be  made  too  rigid.  The  patient  may  have  as  much  bread,  green 
vegetables,  and  potatoes  as  he  likes  ;  several  teaspoonfuls  of  levu  - 
lose  daily  will  help  to  keep  him  alive.  It  is  of  paramount  im- 
portance to  promote  the  excretion  of  toxins  by  favoring  free  diu- 
resis. The  patient  is  allowed  to  drink  as  much  water  as  he  chooses, 
and  we  especially  recommend  a  generous  daily  supply  of  the  cus- 
tomary alkaline  table-waters,  charged  with  free  carbonic-acid  gas. 
Strong  acids  ought  not  to  be  given  ;  nor  are  large  amounts  of 
alkalies  to  be  recommended  for  long  periods  ;  if  large  enough  to 
decrease  the  acidosis  considerably,  they  cause  digestive  troubles 
and  have  a  weakening  effect.  It  is  also  most  important  to  keep 
the  bowels  open  by  means  of  massage,  aperient  drugs,*  or  by  in- 
jections. The  latter  are  advantageously  performed  with  large  quan- 
tities of  tepid  water  and  enough  potassium  permanganate  to  pro- 
duce a  faint  violet  color  in  the  water. 

Whenever  there  is  a  danger  of  coma,  great  care  must  be  observed 
in  the  use  of  narcotic  and  somniferous  remedies. 

When  the  prodromes  appear,  or  if  headache  and  great  lassitude 
raise  suspicion  of  coma,  rapid  measures  may  still  afford  some 
respite.  The  patient  is  at  once  put  to  bed,  receives  a  glass  of 
brandy  or  of  whisky,  or  a  subcutaneous  injection  of  ether,  and  is 
given  enormous  amounts  of  sodium  bicarbonate  in  some  water  rich 

*  I  often  give  : 

Pulveris  aloes,   "1 

Pulveris  rhei,     J       4      s- 

Extract,  colocynth.  comp., 3        gm. 

Extract,  hyoscyamus, 1. 50  gm.  M. 

Ft.  pil.  No.  Ix. 

SiG. — One,  two,  or  three  pills  at  night. 
The  aperient  effect  of  these  pills  usually  follows  in  the  morning. 


TREATMENT.  259 

in  free  carbonic  acid.  A  moderate  dose  of  digitalis  or  strophanthus 
may  also  be  administered.  The  patient  may  also  take  a  bath  at  a 
temperature  of  38°  or  39°  C.  (100.4°  o^  101.2°  F.). 

If  matters  have  progressed  still  further, — if  the  respiration  is 
dyspneic,  the  pulse  inordinately  frequent, — the  same  steps  must  be 
taken  ;  except  in  exceedingly  rare  cases  neither  they  nor  any  other 
means  will  effect  more  than  a  transitory  and  fallacious  improve- 
ment. Under  such  circumstances  the  alkali?ie  solution  may  be  in- 
jected into  a  vein,'*  but  this  can  not  be  considered  necessary,  as  it 
presents  few  advantages  over  administration  of  large  amounts  of 
alkali  by  the  mouth,  and  its  effects  are  almost  always  of  short 
duration.  The  intravenous  injection  of  an  alkaline  solution  requires, 
besides,  elaborate  contrivances,  and  is  but  rarely  undertaken  in 
private  practice.  Stadelmann  used  a  concentrated  solution  of  sodium 
bicarbonate  and  citric  acid,  and  injected  150  cu.  cm.  three  or  four 
times  a  day.  Others  use  solutions  of  a  mixture  of  sodium  chlorid, 
bicarbonate,  phosphate,  and  sulphate.  Lepine  dissolves  7  grams 
of  sodium  chlorid  and  10  grams  of  sodium  bicarbonate  in  a  liter  of 
water ;  injects  slowly,  but  within  a  short  while,  2  liters  ( !  ! )  of  this 
solution  at  a  temperature  of  38°  C.  (100.4°  F.)  into  a  vein  of  the 
arm. 

Whether  the  intravenous  injection  be  performed  or  not,  a  concen- 
trated solution  of  sodium  bicarbonate  in  large  doses  should  always 
be  given  by  the  mouth,  and  a  subcutaneous  injection  of  ether  or 
caffein  citrate  may  also  be  given. 

The  immediate  effect  of  the  alkaline  venous  injections,  or  of 
large  doses  of  sodium  bicarbonate  by  the  mouth,  is  sometimes 
apparently  favorable,  and  likely  to  inspire  the  inexperienced  with 
the  hope  that  the  patient  will  return  to  his  previous  state  before  the 
onset  of  the  symptoms  of  coma.  In  the  large  majority  of  cases 
this  improvement  will  last  only  for  a  few  hours  or  for  a  couple  of 
days,  and  the  physician  will  do  well  to  prepare  those  interested  for 
the  patient's  approaching  death,  however  strongly  the  comatose 
symptoms  have  receded  for  the  moment. 

In  treating   a  case   of  diabetes    our   first  duty — apart  from   the 

*  The  subcutaneous  injection  of  large  amounts  of  alkaline  solution  presents  far 
greater  inconveniences  and  dangers  than  advantages,  and  ought  never  be  practised. 


26o  DIABETES    MELLITUS    AND    GLYCOSURIA. 

almost  always  hopeless  task  of  removing  the  cause  of  the  dystrophy 
— is  to  protect  the  patient  from  the  inanition  that  threatens  from  the 
loss  of  glucose.  Next  in  importance  is  the  task  of  providing 
a  sufficient  number  of  calories  in  such  food  as  to  cause  the  least 
possible  hyperglycemia  and  blood  toxins,  and  counteract,  as  much 
as  possible,  the  development  of  the  diabetes.  Dietetic  prescriptions 
will  thus  always  constitute  an  important  part  of  the  treatment,  though 
they  ought  not,  as  is  often  the  case,  to  make  up  the  whole  treatment. 
The  facts  that  ought  to  form  the  basis  for  our  views  on  the  dietary 
for  a  diabetic  are  as  follows  : 

1.  An  individual  performing  some  mechanical  work  needs  from 
thirty-five  to  forty  calories  per  kilogram  of  bodily  weight  in  twenty- 
four  hours  to  maintain  his  nutritive  balance. 

2.  Proteids  yield  3.2,  fats  8.4,  and  carbohydrates  3.8  net  calories 
per  gram  in  healthy  persons,  and  usually  as  much  in  diabetics — 
minus  the  loss  from  glucose  in  the  urine  following  the  ingestion  of 
carbohydrates  in  the  mild  stage,  and  present  with  any  diet  during 
the  severe  stage,  of  the  diabetic  dystrophy. 

3.  Carbohydrates  ingested  in  ordinary  amounts  cause  in  all  cases 
of  diabetes  the  distinctly,  though  only  slightly,  injurious  hypergly- 
cemia, which  finds  its  expression  in  the,  pei'  se,  almost  indifferent 
glycosuria. 

4.  All  diabetic  patients,  however,  utilize  some  portion  of  ingested 
carbohydrates,  and  the  calories  thus  gained  contribute  better  than 
calories  derived  from  fat  to  the  protection  of  the  organism's  own 
proteids.  Levulose  is  better  utilized  than  any  other  yet  known 
and  fully  acknowledged  carbohydrate. 

5.  Restriction  of  carbohydrates  in  the  food  causes  a  decrease  or 
a  cessation  of  hyperglycemia  and  glycosuria,  and,  apart  from  other 
advantages,  counteracts  the  development  of  the  glycosuric  dys- 
trophy. 

6.  Fat,  ingested  in  any  quantity,  does  not  cause  hyperglycemia 
or  glycosuria  in  any  stage  of  diabetes. 

7.  Fat,  however,  in  spite  of  its  high  caloric  value,  can  not  be 
ingested  in  any  quantity  that  even  remotely  covers  the  expenses  of 
the  organism. 

8.  Still,  fat  can  be  ingested  in  much  larger  quantity  with  than 
without  the  ingestion  of  carbohydrates. 


TREATMENT.  26 1 

9.  In  cases  of  severe  diabetes  toxins  arise  in  the  blood  that  are 
far  more  injurious  that  the  hyperglycemia. 

10.  These  toxins  are  increased  by  exclusion  or  too  rigid  a 
restriction  of  carbohydrates  from  the  food. 

11.  Normal  human  food — apart  from  water  and  salts — consists 
of  proteid,  fat,  and  carbohydrate,  and  permanent  exclusion  of  car- 
bohydrate from  the  diet  can  not  be  effected,  because  it  prevents  the 
supply  of  a  sufficient  quantity  of  calories  and  causes  severe  dis- 
turbances of  the  digestive  functions. 

12.  Among  articles  of  food  rich  in  carbohydrate  bread  is  most 
difficult  to  exclude. 

A  rational  diet  for  a  diabetic  must  be  founded  on  all  these  facts  ; 
if  too  much  importance  be  attached  to  dangers  or  to  advantages 
of  any  special  kind,  the  treatment  necessarily  will  be  defective. 

An  absolute  diet — by  which  I  mean  a  diet  of  meat  and  fat  with 
the  strictest  possible  exclusion  of  carbohydrates — can  never  be 
followed  for  periods  of  more  than  weeks,  or,  at  the  longest,  of 
months.  I  consider  the  correctness  of  this  opinion  to  be  so  univer- 
sally acknowledged  at  the  present  time  that  it  is  unnecessary  to 
spend  more  words  on  it. 

It  remains,  then,  to  decide  in  which  cases  of  diabetes  it  may  be 
advantageous  periodically  to  exclude  carbohydrates*  from  the  food. 

This  may  advantageously  be  done  in  most  cases  within  the  mild 
diabetic  stage.  Even  with  robust  individuals  in  that  stage,  how- 
ever, I  do  not  find  it  rational  to  prescribe,  nor  could  I  prevail  upon 
the  patient  to  submit  to,  longer  periods  of  absolute  diet  than  a 
month. 

The  advantages  of  the  absolute  diet  in  mild  cases  consist  in  the 
cessation  of  the  hyperglycemia  and  its  effects,  the  cessation  in  itself 
counteracting  the  progressive  tendency  of  the  diabetes  and  often 
increasing  the  power  of  assimilating  carbohydrates. 

The  disadvantages  of  the  absolute  diet,  even  in  mild  cases,  are. 


*  Unfortunately  for  diabetics,  bread  is  the  kind  of  food  that  most  people  find  it  most 
difficult  to  spare.  If  any  one  should  for  a  time  live  on  only  two  of  the  three  kinds  of 
food, — meat,  butter,  and  bread, — he  would  want  first  of  all  the  bread  and  resign  the  butter. 
It  is  also  known  that  large,  fairly  civilized  populations  chiefly  (and  up  to  more  than  90 
per  cent,  of  the  whole  solid  food)  live  on  rice,  but  meat  and  fat  nowhere  constitute  so 
large  apart  of  the  food,  except  among  the  few  and  low-ranking  tribes  in  the  Arctics. 


262  DIABETES    MELLITUS    AND    GLYCOSURIA. 

unfortunately,  very  great.  The  patients  with  this  diet  often  suffer 
from  constipation,  which  is  likely  to  give  way  only  to  diarrhea.  They 
lose  their  appetite  and  are  not  able  to  ingest  much  fat  or  enough 
of  any  permitted  food  to  maintain  their  nutritive  balance  ;  they  almost 
invariably  lose  flesh.  The  neurasthenic  symptoms,  rarely  absent 
in  cases  of  diabetes,  are  especially  prone  to  be  aggravated  by  the 
inanition.  The  mere  absence  of  normal  pleasure  and  satisfaction  at 
meals  also  has,  in  many  cases,  an  unfortunate  effect  on  the  patient's 
mental  state. 

It  will  generally  be  found  that  the  patient  will  bear  better  the 
absolute  diet,  and  derive  greater  advantages  from  it,  the  fatter  and 
the  less  nervous  he  is.  The  state  of  the  digestive  organs  and  their 
power  to  support  the  absolute  diet  is  also  a  most  important  and 
a  most  varying  factor.  It  must  also  be  remembered  that  there  are 
in  apparently  quite  similar  cases  great  individual  differences  in  the 
capability  of  supporting  and  in  the  general  effects  of  the  absolute 
diet.  I  have  sometimes,  even  in  mild  cases  of  diabetes,  found  it 
wiser,  after  a  signal  failure,  never  to  prescribe  the  absolute  diet, 
from  which  some  patients  suffer  exceedingly  in  their  general  state 
and  well-being. 

In  the  severe  stage  the  advantages  to  be  derived  from  the  abso- 
lute diet  are  always  much  diminished.  We  can  no  longer  free  the 
patient  from  the  hyperglycemia  and  its  effects,  and  we  can  no 
longer  materially  increase  his  power  of  assimilating  carbohydrates. 
The  disadvantages  arising  from  a  rigid  exclusion  of  carbohydrates 
are  much  greater  than  in  the  mild  stage,  and  the  increase  of  acetone, 
diacetic  acid,  and  ^J-oxybutyric  acid,  inseparable  from  such  a  diet, 
also  directly  increases  the  danger  of  coma,  which,  besides,  becomes 
greater  by  reason  of  the  inanition  itself,  scarcely  to  be  avoided 
upon  exclusion  of  carbohydrates. 

TJie  rational  application  of  these  facts  forbids  the  exclusion  of  car- 
boJiydrates  in  the  distinctly  severe  stage  of  diabetes. 

In  determining  the  daily  allowance  of  carbohydrates  for  a  patient 
in  the  severe  stage  I  must,  however,  distinguish  between  two  classes 
of  patients. 

The  first  class  consists  of  cases  presenting  diacetic  acid  but 
no  ;5-oxybutyric  acid  in  the  urine.  There  is  in  these  cases  no 
danger  of  coma  ;  but  the   patients   generally  have   lost   in  bodily 


TREATMENT.  263 

weight,  and  are  in  a  poor  state  of  general  health.  An  exclusion  of 
carbohydrate  seems  to  me,  even  in  these  cases,  to  do  more  harm 
than  good,  by  decreasing  their  bodily  weight  and  by  exerting  a  bad 
influence  on  the  general  somatic  and  mental  state.  I  customarily 
allow  such  patients  from  eighty  to  one  hundred  grams  of  carbohy- 
drate in  twenty-four  hours  ;  usually,  at  least  half  of  this  portion  is 
taken  in  bread  and  the  rest  in  vegetables  of  different  kinds  (see 
below). 

The  second  class  of  severe  cases  consists  of  those  in  whose  urine, 
in  addition  to  diacetic  acid,  also  /3-oxybutyric  acid  is  present:  i.  e., 
cases  in  constant  danger,  more  or  less  pronounced,  of  coma. 
Whenever  I  encounter  a  diabetic  patient  in  the  distinctly  severe 
stage,  I  allow  him  a  moderate  daily  amount  of  carbohydrates 
(eighty  grams)  until  I  have  acquired  definite  information  on  this 
point.  If  after  the  removal  of  all  sugar  from  the  urine  by  fermen- 
tation, and  of  combined  (levogyrate)  glycuronic  acids  by  precipitation 
with  lead  acetate  and  ammonia,  I  still  find  distinct  levogyration, 
denoting  the  presence  of  /J-oxybutyric  acid  and  at  the  same  time 
an  advanced  "  acidosis  "  (in  the  blood),  I  am  averse  to  any.great  re- 
striction of  carbohydrates.  However  absolutely  I  condemn  an  ex- 
clusion, if  ever  so  short,  of  carbohydrates  in  these  cases,  I  am 
willing  to  admit  that  the  rational  daily  amount  of  carbohydrate  is 
a  matter  open  to  discussion.  Considerable  experience,  however, 
both  of  the  effect  of  my  own  dietetic  system  and  of  that  of  other 
physicians,  has  forced  me  to  the  conclusion  that  I  promote  best  the 
interests  of  such  patients  by  allowing  them  a  generous,  if  not  an 
unlimited,  amount  of  bread  *  and  potatoes.  I  exclude  from  their 
dietary  only  such  articles  as  contain  much  carbohydrate  and  at  the 
same  time  can  easily  be  spared  (rice,  macaroni,  peas,  dried  or  sweet 
fruits,  sugar  and  sweets,  champagne,  beer,  sweet  wines  and  liquors, 
etc.).  In  these  cases,  if  circumstances  permit,  I  also  use  levulose, 
recommending  it  strongly  as  a  substitute  for  cane-sugar.  It  in- 
variably increases  the  glycosuria,  but  as  invariably  diminishes  the 
autophagy  and  loss  of  weight,  and  I  believe  that  it  has  in  many  of 
my  own  cases  postponed  the  final  issue. 


*  In  cases  with  advanced  acidosis  I  allow  at  least  one  hundred  grams  of  ordinary 
white  bread  a  day. 


264  DIABETES    MELLITUS    AND    GLYCOSURIA. 

If  a  patient  in  the  advanced  severe  stage  is,  after  some  allowance 
of  carbohydrate  in  his  food,  put  on  an  exclusive  animal  regime,  or 
only  allowed  a  small  daily  amount  of  carbohydrate,  he  frequently 
is  attacked  and  killed  by  coma  within  a  few  days. 

"  But,"  some  one  will  say,  "  the  absolute  diet  has  also  a  diagnostic 
purpose  ;  and  how  shall  I  ascertain  the  state  of  the  patient's  dystro- 
phy without  putting  him  on  an  exclusive  animal  diet,  with  a 
minimum  of  carbohydrate  ?  "  I  have  already  answered  this  objection. 
If  a  diabetic  patient  on  a  mixed  diet  passes  urine  that  does  not 
yield  a  distinct  Gerhardt's  reaction  (a  wine-red  color  on  addition  of 
a  solution  of  ferric  chlorid),  I  may,  without  danger  of  coma,  with- 
draw the  carbohydrate.  If  the  urine  presents  a  distinct  Gerhardt's 
reaction,  the  case  is  a  severe  one,  and  it  would  be  a  grave  error  to 
put  him  on  an  absolute  diet.  / 

In  my  opinion  we  must  adopt  the  rule  in  all  cases  of  diabetes, 
mild  or  severe,  never,  as  a  permanent  dietetic  rule,  to  put  any 
maximum  limit,  any  restriction,  on  the  supply  of  meat  or  fat.  There 
are  cases  on  the  borderland  between  mild  and  severe  diabetes  that 
with  exclusion  of  carbohydrates  and  some  restriction  of  meat  pre- 
sent no  glycosuria,  and  that  with  exclusion  of  carbohydrates,  but 
with  a  larger  supply  of  meat,  excrete  small  quantities  of  glucose. 
A  restriction  of  meat  also  in  many  other  cases  diminishes  the 
glycosuria.  The  slight  corresponding  hyperglycemia,  however,  is 
an  insignificant  matter  as  compared  with  too  much  prescribing  and, 
above  all,  with  underfeeding.  When  one  of  Germany's  greatest 
clinicians  and  best  authorities  on  diabetes  (Naunyn)  recommends  a 
maximum  limit  in  the  supply  of  meat,*  even  with  an  exclusion  of 
carbohydrates, — which  he  also  prescribes  in  cases  in  the  severe  stage, 
— with  all  my  admiration  for  him  personally  and  for  his  work,  I  can 
not  follow  him  here.  How  could  a  patient  who  has  to  live  exclu- 
sively on  meat  and  fat  avoid  underfeeding  if  he  is  not  permitted, 
even  with  regard  to  this  poor  food,  to  satisfy  his  appetite,  which  on 
this  point  affords  more  trustworthy  indications  than  are  sometimes 
given  by  learned  and  otherwise  clever  physicians  ? 

The  danger  from  underfeeding  with  exclusion  or  strong  restric- 


*  So  far  as  I  know,  Rollo  was  the  first  to  urge  a  restriction  even  of  proteids  in  cases 
of-  diabetes.     I  have  no  doubt  that  this  dietetic  principle  is  at  present  on  its  last  legs. 


TREATMENT. 


265 


tion  of  carbohydrates  is  always  imminent,  and  rather  than  restrict 
proteids  and  fat,  we  ought  as  much  as  possible  to  insure  the  patient 
against  receiving  too  small  amounts  of  both  for  the  maintenance  of 
his  nutritive  equilibrium.  Even  when  we  do  our  best,  we  shall  find 
that  a  marked  restriction  of  carbohydrates  often  necessarily  results 
in  some  degree  of  starvation. 

Let  us  consider  the  dietetic  needs  of  a  man  of  seventy-five  kilo- 
grams of  bodily  weight  who  receives  forty  calories  per  kilogram  in 
twenty-four  hours,  and  how  to  meet  those  needs  with  different  pro- 
portions of  the  three  great  classes  of  food.  I  shall,  as  far  as  possi- 
ble, confine  myself  to  round  figures  in  making  the  whole  amount  of 
the  daily  supply  reach  about  3000  calories  : 


Case. 

Proteid. 

Net  Value, 
3.2  Cal. 

Fat. 

Net  Value, 
8.4  Cal. 

Carbohy- 
drate. 
Net  Value, 
i^.8  Cal. 

Sums  of  Calories. 

No.  I 

135  gra. 

80  gm. 

500  gm. 

=  432  -f  672  +   1900  =  3004 

"  2 

420  " 

200  " 

0  " 

=  1344  -f  1680  -f    0  =  3024 

"  3 

120  " 

285  " 

60  " 

=  384  -f  2394  +  228  =  3006 

"  4 

700  " 

65  " 

60  " 

=  2240  -|-  546  -)-  228  =  3014 

"  5 

185  " 

260  " 

60  " 

=  592  -|-  2184  -f  228  =  3004 

"  6 

225  " 

245  " 

60  " 

=  720  +  2058  -|-  228  =  3006 

"  7 

250  " 

235  " 

60  " 

=  800  -|-  1974  -|-  228  =  3002 

"  8 

345  " 

200  " 

60  " 

=  1 104  +  1680  -f  228  =  3012 

"  9 

300  " 

200  " 

100  " 

=  960  -j-  1680  -|-  380  =  3020 

"  10 

190  " 

240  " 

100  " 

=    608  +  2016  -f-  380  =  3004 

The  first  line  in  the  table  shows  an  arrangement  that  gives 
fifteen  grams  more  of  proteid  and  twenty-five  grams  more  of  fat 
with  the  same  amount  of  carbohydrate  than  Voit's  classic  table. 
I  have  made  the  additions  necessary  to  reach  the  3000  calories  to 
the  proteids  and  to  fat,  because  the  patient,  of  his  own  choice,  fol- 
lowing only  the  dictates  of  taste,  is  much  more  likely  to  do  this 
than  to  increase  the  amount  of  carbohydrate  above  500  grams. 
Among  Anglo-Saxon  and  Teutonic  nations  the  free  choice  of  pro- 
portions for  3000  calories  would  often  increase  the  proteids  to  at 
least  150  grams,  and  the  fat  to  an  equally  large  or  even  larger 
amount. 


266  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  second  line  in  the  table  shows  at  a  glance  how  very  difficult 
it  is  to  obtain  the  3000  calories  without  carbohydrate.  If  we  put  the 
fat  at  200  grams, — which  for  many  individuals  represent  the  maxi- 
mum possible  of  ingestion,  and  which  are  contained  in  about  240 
grams  of  butter, — we  must  take  420  grams  of  proteid  or  nearly  1250 
grams  of  cooked  meat  (free  from  fat).  If  we  trust  to  the  ability  of 
the  patient  to  take  daily  ten  eggs,  each  of  which  shall  contain  fifty 
grams  of  food,  we  may  decrease  the  meat  by  about  200  grams,  and 
the  butter  by  about  fifty-four  grams  ;  but  how  many  individuals  are 
able  to  eat  fully  a  kilogram  of  meat,  nearly  ■§-  of  a  kilogram  of  butter, 
and  ten  eggs  a  day,  even  if  the  most  expert  chefs  put  their  heads 
together  to  make  the  whole  as  palatable  as  possible  ? 

The  third  and  the  fourth  lines  in  the  table  only  show  that, 
even  if  I  allow  sixty  grams,  or  the  minimum  of  carbohydrate  that  is 
necessary  in  the  long  run,  by  increasing  only  the  proteids  or  only 
the  fat,  I  obtain  perfectly  impossible  quantities  of  the  one  or  the 
other. 

The  fifth,  sixth,  seventh,  and  eighth  lines  represent  the  possi- 
bilities of  ingesting  enough  of  proteids  and  fat  in  addition  to  the 
necessary  minimum  of  carbohydrate  ;  but  we  find  that  however  the 
proportions  of  proteids  and  fat  are  arranged,  the  patient  is  likely  to 
have  before  him  a  difficult  task. 

The  ninth  and  tenth  lines  show  how  the  patient's  task  is  facili- 
tated by  allowing  him  a  somewhat  larger  amount  of  carbohy- 
drate. There  are  a  great  many  persons  of  75  kilograms  of  bodily 
weight  who  are  able  to  keep  themselves  in  a  fair  state  of  health  by 
ingesting  in  the  twenty -four  hours  190  grams  of  proteids,  240 
grams  of  fat,  and  100  grams  of  carbohydrate,  or  about  2.5  grams 
of  proteid  and  3.2  grams  of  fat  per  kilogram  bodily  weight.  The 
quantity  of  fat  is  rather  large ;  in  many  cases  it  will  be  necessary  to 
diminish  this  and  to  increase  the  amount  of  proteids  to  something 
more  like  the  quantities  given  in  the  ninth  column.  But  the  more 
fat  a  diabetic  can  ingest,  the  better  off  he  is,  and  a  patient  of  75 
kilograms  ought,  if  possible,  not  ingest  less  than  200  grams  of  it. 
The  ninth  and  tenth  lines  show  proportions  that,  especially  in 
mild  cases,  will  often  be  found  in  the  long  run  to  be  the  most 
advantageous.  In  very  severe  cases  100  grams  of  carbohydrate  are, 
for  a  person  of  this  weight,  never  too  much,  but  often  too  little. 


TREATMENT.  26/ 

In  this  table  I  have  not  taken  into  consideration  the  loss  of  calo- 
ries represented  by  the  glucose  in  the  urine.  On  the  other  hand,  I 
have  not  taken  into  consideration  the  calories  that  may  be  gained 
by  the  use  of  a  moderate  amount  of  alcohol.  If  we  put  the 
caloric  value  of  glucose  at  3.7  per  gram,  we  find  that  a  patient  that 
passes  50  grams  of  glucose  in  the  twenty-four  hours — a  large 
amount  in  the  mild  stage  with  a  daily  supply  of  100  grams  of  car- 
bohydrate— loses  185  calories  of  what  he  has  ingested  and  digested. 
This  loss  is  not  larger  than  the  allowance  of  alcohol — equivalent  to 
7  calories  per  gram — that  can  be  accorded  to  a  person  of  75  kilo- 
grams. 

Rollo  was  the  first,  in  the  beginning  of  this  century,  to  recommend  an  exclu- 
sive diet  of  meat  and  fat  in  cases  of  diabetes.  He  committed  the  error,  after- 
terward  repeated  by  others,  of  prescribing  a  restriction  even  of  meat.  In 
those  days  the  laws  of  nutrition  and  the  organism's  imperative  demands  for 
a  certain  number  of  calories  were  not  known,  and  importance  was  attached 
almost  exclusively  to  a  removal  of  the  glycosuria.  Rollo,  however,  in  his 
practice  did  not  carry  out  his  theories  with  regard  to  an  exclusively  animal  diet, 
which,  according  to  his  prescription,  was  adopted  throughout  Great  Britain  and 
its  colonies,  and  soon  spread  to  France  and  Germany.  Wherever  this  system 
was  introduced  it  proved  unsatisfactory,  from  the  consequent  disturbances  of 
digestion,  its  manifest  insufficiency,  and  from  the  patient's  invariable  aversion. 
Opinions  on  this  subject  have  since  been  much  divided,  and  are  so  to  some 
extent  at  the  present  time.  Bouchardat  (from  1842)  contributed  largely  to  the 
establishment  of  a  better  system  with  a  mixed  diet  of  ingestable  quantities  of 
meat  and  fat,  and  a  restricted  supply  of  starch,  chiefly  taken  in  the  form  of  green 
vegetables  and  bread  ;  he  also  allowed  moderate  quantities  of  alcohol.  Mean- 
while, Prout  introduced  gluten-bread  and  inaugurated  the  long  series  of  breads 
made  especially  for  diabetics. 

The  late  distinguished  Neapolitan  physician,  Cantani,  was  one  of  the  most 
energetic  advocates  in  our  time  of  an  absolute  (animal)  diet  for  cases  of  dia- 
betes. He  allowed  only  meat  and  fat,  and  as  representatives  of  the  latter  he 
recommended  olive  oil  and  cod-liver  oil.  Butter  was  forbidden  because  it  con- 
tains a  trace  of  milk-sugar.  Cantani  later  became  somewhat  more  reasonable, 
and  allowed  butter  and  "fruttt  di  mare,'''  a  dish  composed  of  different  small 
salt-water  animals,  some  of  which  contain  a  considerable  percentage  of  gly- 
cogen. It  was  his  plan  to  enforce  this  diet  for  at  least  three  months,  and  then 
gradually  to  make  concessions  toward  a  more  mixed  food.  One  gains  quite  a 
curious  impression  from  reading  Cantani's  opinions  with  regard  to  the  possi- 
bilities and  the  effects  of  the  severe  regime  he  prescribed.  I  suspect  that  some 
of  his  patients  have,  without  his  knowledge,  smuggled  not  inconsiderable 
quantities  of  macaroni  into  their  food.  Cantani  spent  his  life  in  Naples,  with 
its  heavenly  nature  and  vile  population,  by  whom  a  true  word,  to  quote  Swin- 
burne, in  "  Peter  Simple,"  seems  to  be  spoken  only  by  mistake. 


268  DIABETES    MELLITUS    AND    GLYCOSURIA. 

An  absolute  diet  in  the  severe  stage  of  diabetes  is  now  insisted  upon  strictly 
by  Naunyn  and  his  school.  Even  his  justly  honored  name  is  not  sufficient  to 
sustain  this  position.  The  cases  published  by  him  and  his  disciples  demon- 
strate what  this  regime  is  capable  of  effecting  in  the  severe  stage ;  the  patients 
immediately  after  its  inception  being  often  delivered  from  their  sufferings  by 
death  in  coma. 

It  is  a  pleasure  to  know  that  the  absolute  diet  has  certainly  never  been 
observed,  except  for  a  very  short  time,  by  any  one  not  kept  under  lock  and 
key.  A  considerable  experience  with  cases  of  diabetes  in  representatives  of 
the  best  nations  and  of  the  best  (z.  e.,  most  educated,  most  intelligent,  and 
therefore  most  reliable  and  obedient)  classes,  has  taught  me  that  the  physician, 
even  if  he  knows  how  to  acquire  the  confidence  of  his  patients,  can  only  rarely 
enforce  abstinence  from  carbohydrates  (bread)  for  as  long  time  as  a  month,  and 
that  any  one  by  unreasonable  demands  in  this  respect  only  incurs  the  danger 
of  not  being  obeyed  even  in  feasible  matters. 

Experience  no  less  than  late  advances  in  physiology  and  experimental 
pathology  should  prevent  us  from  permitting  our  fears  of  hyperglycemia  with 
its  glycosuria  to  overshadow  other  and  greater  dangers. 

There  died  in  Sweden  some  years  ago  a  man  whose  case  is  an  illustration 
of  the  comparatively  insignificant  danger  of  hyperglycemia.  The  patient  was 
Professor  Forsell,  well  known  from  his  paper  on  his  own  case,  published  in 
1883.  Forsell  was  no  physician,  and  his  paper  bears  the  stamp  of  the  layman. 
Some  of  his  conclusions  are  entirely  false.  The  facts  with  regard  to  his  diet, 
his  polyuria,  and  his  glycosuria,  however,  are  certainly  in  the  main  correct, 
and  correspond  with  the  data  of  his  physician,  who  died  a  few  years  ago. 
Forsell's  diabetes  began  quite  suddenly  in  1866;  the  same  year  the  percentage 
of  sugar  reached  7.4,  the  polyuria  6.5  liters,  the  specific  gravity  1.040,  the  daily 
loss  of  glucose  often  425  grams,  and  on  one  occasion  850  grams.  Professor 
Forsell  never  was  my  patient,  and  I  am  not  familiar  with  the  details  of  his 
case  ;  but  although  its  course  proves  it  to  have  remained  at  least  for  a  consider- 
able length  of  time  in  the  mild  stage,  there  is  no  doubt  that  it  was,  in  1866, 
already  quite  an  intense  diabetes.  His  physician  at  first  put  him  on  a  strict 
diet;  unfortunately,  there  is  no  record  of  its  effect  on  the  glycosuria.  Forsell, 
however,  soon  found  that  the  strict  diet,  besides  being  exceedingly  unpleasant, 
always  made  him  feel  ill  and  weak.  Having  ascertained  the  evil  consequences 
of  this  system,  he  adopted  the  opposite  extreme,  consuming  a  considerable 
amount  of  bread  and  of  vegetables,  and  every  day  drinking  from  6  to  8  pints 
of  Bavarian  beer.  "  By  avoiding  diet,  watering-places,  and  medicine,  I  have 
kept  in  very  fair  health  since  1873,"  Forsell  writes  in  1883.  When  Forsell  died, 
he  had  suffered  from  most  pronounced  diabetes  for  about  twenty  years.  Such 
a  prolongation  of  life  in  cases  of  this  kind  is  extremely  rare — much  rarer  than 
it  is  for  a  gouty  person  with  mild  diabetes  to  live  for  forty  years.  Is  there 
any  reason  for  believing  that  Forsell's  life  would  have  been  longer  or  happier 
if  he  had  lived  on  meat  and  fat,  without  carbohydrate  or  with  a  scanty  supply  ? 

I  am  particularly  anxious  not  to  be  accused  of  approving  of  Forsell's 
regime.  I  am  perfectly  certain  that  he  might,  with  advantage,  have  made  some 
restrictions  in  carbohydrate — and  no  one  will  approve  of  his  enormous  consump- 


TREATMENT.  ,269 

tion  of  Bavarian  beer.  The  mere  fact,  however,  that  a  diabetic  of  this  kind  can 
live  in  fairly  good  health  and  do  fairly  good  work  for  more  than  twenty  years 
is  worthy  of  consideration,  and  may  afford  a  foundation  for  conclusions  that, 
however  prudently  formulated,  are  of  great  practical  portent.  Professor  For- 
sell's  was  far  from  being  a  good  regime,  but  I  feel  convinced  that  if  I  had  to 
choose  for  my  patients — as  a  rule,  for  years — between  his  regime  and  an  exclu- 
sion or  a  severe  restriction  of  carbohydrates,  I  should  act  wisely  in  choosing 
the  former. 

In  the  mild  stage  we  always  have  to  put  a  maximum  limit  upon 
the  daily  amounts  of  carbohydrate.  Except  in  dealing  with  a  cer- 
tain kind  of  hypochondriacal  patients,  we  need  not  trouble  our- 
selves with  regard  to  a  minimum  limit.  In  the  enormous  majority  of 
cases  we  may  feel  certain  that  if  the  patient  does  not  consume  more 
carbohydrate  than  we  prescribe,  he  will  hardly  ever  consume  less. 

In  a  large  number  of  cases  the  rational  daily  allowance  of  carbo- 
hydrate is  represented  by  the  maximum  that  the  patient  can  take 
without  the  development  of  glycosuria.  We  should  never  restrict 
the  patient's  allowance  of  carbohydrate  below  the  amount  that 
leaves  him  free  from  sugar  in  his  urine,  and  thus  free  from  any  dis- 
tinct hyperglycemia.  Whenever  a  patient  can  take  the  necessary 
amount  of  carbohydrates  for  the  maintenance  of  good  digestive 
action  and  nutritive  equilibrium,  without  the  development  of  glyco- 
suria, he  is  permitted  to  take  that  amount.  According  to  my 
experience,  the  minimum  amount  sufficient  in  the  long  run  for  a 
full-grown  person  is  hardly  ever  less  than  60  grams  of  carbohy- 
drate, and  is  usually  somewhat  more.  On  the  other  hand,  it  is 
rarely  necessary  to  give  a  diabetic  patient  in  the  mild  stage  more 
than  100  grams  of  carbohydrate  ;  neither  is  he  capable  of  taking 
more  for  any  great  length  of  time  without  the  development  of 
glycosuria.  The  rational  daily  allowance  of  carbohydrate  for  pro- 
tracted periods  for  a  patient  in  the  mild  stage  thus  varies  usually 
from  60  to  100  grams.  For  reasons  mentioned  in  the  preceding 
chapter,  it  is  well  to  determine  the  amount  in  each  case  by  giving 
the  patient  the  larger  quantity  (100  grams)  and  diminishing  it  until 
the  glycosuria  ceases,*  or  until  the  necessary  minimum  (of  about  60 
grams)  for  constant  use  has  been  determined. 

*We  consider  the  glycosuria  practically  to  have  ceased  when  Nylander's  and  Feh- 
ling's  solutions  react  only  faintly  with  a  sample  of  the  urine  collected  during  twenty- 
four  hours. 


2/0  DIABETES    MELLITUS    AND    GLYCOSURIA. 

If  the  patient  (in  the  mild  stage)  continues  to  exhibit  glycosuria 
when  his  daily  allowance  of  carbohydrate  is  restricted  to  the  mini- 
mum necessary  for  maintaining  good  digestive  activity  and  nutritive 
equilibrium,  it  is  preferable  to  risk  the  moderate  disadvantages  of 
the  slight  corresponding  hyperglycemia  rather  than  the  more  serious 
dangers  of  digestive  disturbances  and  inanition.  The  rational  daily 
allowance  of  carbohydrate  varies  not  only  among  individuals,  but 
also  from  time  to  time  in  the  same  individual.  Sometimes  loss  of 
appetite  or  of  flesh,  exacerbation  of  neurasthenic  symptoms,  mental 
inability  to  submit  to  some  restrictions,  force  us  to  make  some  con- 
cessions. In  cases  complicated  by  gout,  the  hope,  always  faint,  of 
bringing  about  recovery  from  the  diabetes  by  removing  the  hyper- 
glycemia is  lost.  The  chances  that  the  diabetes  will  remain  mild 
are  almost  certain,  and  we  are  not  inclined  to  be  severe,  especially 
as  we  have  no  wish  to  increase  too  greatly  the  proteids,  and 
thus  to  put  a  strain  on  the  kidneys,  and  as  we  need  bread  to 
facilitate  the  ingestion  of  the  necessary  amount  of  fat.  The  further 
advanced  in  age  the  patient,  the  less  danger  there  is  of  his  ever 
reaching  the  severe  stage  of  diabetes,  and  we  can  afford  to  be 
more  liberal ;  in  senile  cases  we  never  urge  severe  restrictive 
measures. 

If,  on  the  other  hand,  there  is  reason  to  believe  a  case  of  diabetes 
to  be  of  quite  recent  origin,  we  should  always  estimate  at  its  full 
value  the  increased  chance,  however  small,  of  perfect  recovery  by 
removal  of  the  hyperglycemia,  and  for  a  long  while  we  restrict  the 
carbohydrate  as  much  as  possible.  During  healing  processes  of  all 
kinds,  or  before  an  operation,  it  is  also  desirable  to  remove  as  much 
as  possible  the  hyperglycemia.  Finally,  a  sudden  decline  in  a 
diabetic  patient's  power  of  assimilating  carbohydrate  makes  a  rigid 
restriction  necessary. 

In  those  cases  in  the  mild  stage  in  which  the  patient's  power  of 
assimilating  carbohydrate  is  too  low  to  permit  of  the  usual  diminu- 
tion of  his  daily  allowance  below  his  limit  of  assimilation  and  of 
the  removal  of  his  hyperglycemia  there  remain  several  ways  of 
mitigating  the  hyperglycemia  and  its  effects. 

For  this  purpose  the  patient  may  be  advised  to  take  his  whole 
daily  allowance  of  carbohydrate  during  his  first  one  or  two  meals 
of  the  day  ;  the  physician  should  not  forget  to  insist  that  he  shall 


TREATMENT.  2/1 

at  the  same  time  take  as  much  butter  as  possible  with  his  bread. 
By  entirely  excluding  or  markedly  restricting  the  carbohydrates  of 
the  last  meal  the  hyperglycemia  also  is  excluded  or  restricted 
during  the  larger  part  of  the  twenty-four  hours.  The  last  meal, 
thus  consisting  exclusively  of  animal  food,  will  then  necessarily 
tend  to  be  a  light  one.  The 'German  system,  with  an  early  dinner, 
is  better  for  this  purpose  than  the  custom  prevailing  in  France, 
England,  and  the  United  States,  of  taking  the  heaviest  meal  in  the 
evening. 

There  is  still  another  way  of  mitigating  the  hyperglycemia  and 
its  effects  in  those  cases  in  the  mild  stage  in  which  even  the 
minimum  daily  allowance  of  bread  and  vegetables  necessary  for  the 
maintenance  of  digestive  activity  and  nutritive  equilibrium  cause 
glycosuria  and  hyperglycemia.  For  this  purpose  periods  of  exclu- 
sion or  of  such  severe  restriction  of  carbohydrates  are  prescribed 
that  the  glycosuria,  beyond  faint  traces  in  the  mixed  urine,  dis- 
appears. Such  periods  may  be  prescribed  several  times  a  year  ; 
they  ought  to  last  for  at  least  two  weeks,  but  can  scarcely  ever  be 
enforced  for  more  than  four  weeks.  If  loss  of  weight,  neurasthenic 
symptoms,  and  digestive  disturbances  become  too  marked,  we  have 
to  shorten  these  periods,  which  rarely  pass  entirely  without  some 
of  the  troubles  mentioned.  If  one  prescribes  periods  of  this  kind 
of  as  long  a  duration  as  four  weeks,  he  may  with  advantage  select 
the  summer  for  one  and  the  winter  for  another.  In  the  spring  and 
in  the  autumn  the  tendency  to  mental  depression,  common  among 
diabetics,  is  more  marked,  at  least  in  northern  climates. 

TJie  absolute  or  severe  diet  includes  all  animal  food  except  milk 
(and  its  derivative,  cheese),  with  its  nearly  five  per  cent,  of  lactose, 
and  liver,  with  its  variable,  but  usually  small,  amount  of  glycogen. 
It  thus  allows  all  otherwise  wholesome  parts  of  niamnials,  birds, 
amphibia  (turtles,  frogs,  etc.),  fishes,  lobsters,  crabs,  crazvfish,  oysters, 
etc.  It  would  be  unwise  and  pedantic  to  exclude  from  this 
frugal  dietary  eggs  and  butter,  on  account  of  the  insignificant  pro- 
portion of  carbohydrates  they  contain.  Eggs  are  easily  taken, 
easily  digested,  and,  apart  from  idiosyncrasies,  constitute  an  impor- 
tant item  in  the  severe  diet.  The  butter  with  its  eighty-four  per  cent, 
of  pure  fat  usually  represents  among  Teutons  and  Anglo-Saxons 
the  greater  part  of  the  fat  in  the  food,  and  more  than  is  taken  in 


2/2  DIABETES    MELLITUS    AND    GLYCOSURIA. 

bacon,  meat  of  any  kind,  lard,  olive-oil,  milk,  cheese,  eggs,  etc., 
put  together.  The  butter  tastes  better,  is  more  easily  ingested  and 
digested  than  most  other  fats,  and  has,  besides,  the  great  merit  of 
not  reminding  the  diabetic,  by  any  rarity  of  appearance,  of  his  con- 
dition. It  is  therefore  somewhat  incomprehensible  why  so  many 
diabetics,  except  for  special  indications,  are  tortured  with  that  un- 
palatable fat,  cod-liver  oil.  Neither  can  I  understand  the  superiority 
of  either  olive-oil  or  "  lipanin  "  to  butter,  which  certainly  contrib- 
utes better  than  anything  else  to  the  possibility  of  ingesting  the 
desirable  amount  of  fat.  Unfortunately,  few  persons  are  able  to  take 
large  amounts  even  of  butter  without  bread. 

It  is  a  most  important  rule  to  give  the  patient  with  the  severe  diet 
the  advantage  of  as  great  a  variety  of  food  as  possible,  and  to 
include  different  kinds  of  meat,  birds,  fish,  and  eggs  in  his  dietary. 
When  his  digestive  power  is  weak,  he  often  derives  considerable 
benefit  from  the  modern  condensed  forms  of  proteid  food.  I  have 
especially  often  seen  good  effects  from  the  use  of  "  somatose,  " 
which  is  rich  in  albumoses. 

But  whatever  is  done,  the  patient  will  have  a  trying  time  during 
periods  when  an  exclusively  animal  diet  is  demanded  and  it  is  often 
possible,  even  during  periods  of  rigid  restriction,  considerably  to 
mitigate  his  dietetic  difficulties  by  introducing  into  his  food  small 
quantities  of  those  vegetables  that  contain  comparatively  slight 
amounts  of  carbohydrates.  The  German  ^'  sauerkraut, ^^  the  French 
"  choicer oute,"  when  well  fermented,  does  not  contain  more  than  a 
few  tenths  of  a  per  cent,  of  carbohydrate.  String-beans,  picked 
quite  young  and  before  the  development  of  their  seeds,*  contain 
much  inosite,  but  only  traces  of  carbohydrate.  Lettuce,  cucumbers, 
and  in  many  cases  the  leaves  of  spinacli  may  also  often  be  taken  in 
small  quantities  by  patients  in  an  advanced  mild  stage,  without 
causing  the  appearance  of  more  than  faint  traces  of  glucose  in  their 
urine.  The  mitigation  that  such  an  addition  to  the  dietary  affords 
during  periods  of  severe  restriction  is  often  underrated  by  the 
physician,  but  never  by  the  patient. 


*When  the  seeds  are  developed,  string-beans  contain  several  per  cent,  of  starch  and 
sugar,  and  they  no  longer  constitute  an  appropriate  article  of  food  during  periods  of  rigid 
dietetic  restriction. 


TREATMENT,  2/3 

During  periods  of  anything  like  rigid  restriction  of  carbohy- 
drates, the  diabetic  patient  has  to  choose  between  two  substitutes 
for  bread.  The  one  is  the  genuine,  tasteless,  expensive,  and  almost 
worthless  "gluten-bread,"  of  which  I  have  entirely  abandoned  the 
use.  The  other  substitute  for  bread  is  the  "bread  "  made  accord- 
ing to  Pavy's  and  Seegen's  prescriptions,  of  eggs,  butter,  and 
almonds  deprived  of  their  sugar.  The  almond  bread  which,  as 
bought  in  shops,  usually  contains  starch,  ought  to  be  baked  at 
home,  according  to  the  original  prescription,*  and  can  even  then, 
during  periods  of  severe  restriction,  be  allowed  only  in  small 
amounts. 

The  most  important  question  of  bread,  which  must  be  treated  at 
some  length,  leads  me  to  the  subject  of  the  more  liberal  diabetic  diet, 
in  which  at  least  half,  often  more,  of  the  allowance  of  carbohydrate 
is  given  in  the  form  of  bread.  All  proper  bread  certainly  contains  a 
large  percentage  of  starch,  but  the  human  digestive  apparatus  is  too 
accustomed  to  this  kind  of  food  to  be  able  to  get  along  entirely  with- 
out it.  The  bread,  besides  its  other  nutritive  value,  also  facilitates  the 
ingestion  of  fat,  which,  from  its  high  caloric  value  and  its  properties 
of  not  increasing  either  the  hyperglycemia  or  the  work  of  the  kid- 
neys is  so  advantageous  to  diabetics.  In  discussing  the  question 
of  bread  with  a  diabetic  patient  the  physician  should  never  fail  to 
point  out  its  merit  as  an  excellent  vehicle  for  fat,  and  impose  upon 
him  the  necessity  of  always  taking  butter,  or  butter  and  cheese, 
with  his  bread. 

The  impossibility  of  living  without  bread  and  the  fear  of  its 
starch  for  diabetics  have  led  to  many  attempts  to  produce  for 
these  patients  something  that  might  possess  the  advantages  of 
ordinary  bread  without  supplying  the  much-dreaded  starch.  I  be- 
lieve this  problem  to  be  as  impossible  of  solution  as  the  squaring 
of  the   circle  or  as  the   problem  of  perpetual   motion.     It  is  the 


*  The  powder  of  one-quarter  pound  dried  and  finely  pulverized  almonds  is  put  in  a 
linen  bag  and  cooked  a  quarter  of  an  hour  in  water  with  some  drops  of  vinegar,  then 
well  kneaded  with  three  and  a  half  ounces  of  butter  and  two  whole  eggs.  Then  the 
yolks  of  three  other  eggs  and  some  salt  are  added  to  the  mass.  The  whites  of  the  three 
eggs  are  well  beaten  and  also  added,  whereupon  the  whole  is  put  in  a  buttered  fonn  and 
baked.  When  prepared  in  this  legitimate  way,  without  meal  or  rice,  the  bread  unfortu- 
nately often  lacks  the  proper  consistency. 


2/4  DIABETES    MELLITUS   AND    GLYCOSURIA. 

Starch  in  the  bread  that  chiefly  gives  it  its  good  taste  and  other 
dietetic  merits,  and  that  diabetics,  as  well  as  others,  need.  Every- 
one of  the  many  ^'  breads  for  diabetics''  suffers  from  either  of  two 
faults  :  it  contains  much  starch  or  it  does  not  taste  like  real  bread, 
and  is  a  substitute  for  it  in  almost  nothing  but  name.  Further,  dis- 
honest speculation  has  furnished  the  market  with  a  great  number 
of  preparations  whose  real  qualities  are  concealed  beneath  false  or 
ambiguous  assertions.  At  this  moment  there  is  before  me  a  cir- 
cular from  a  baker,  accompanied  by  a  sample  of  his  aleuronat-bread, 
— the  former  couched  in  such  terms  as  to  make  the  reader  believe 
that  the  ready-made  bread  contains  only  the  comparatively  few  per 
cent,  of  starch  of  the  original  aleuronat,  while  in  reality  it  contains, 
at  the  very  least,  four  times  that  amount.  Patients  easily  persuade 
themselves  that  they  may  consume  any  amount  of  any  bread  that 
is  said  to  be  especially  prepared  for  diabetics.  This  is  the  case 
even  with  the  ordinary  Graham  bread,  which  contains  about  forty 
per  cent.,  by  weight,  of  pure  starch,  or  nearly  eighty  per  cent,  of 
what  is  contained  in  the  same  quantity  of  white  bread.  The  prep- 
arations with  a  small  amount  of  starch  or  with  none  at  all  are 
tasteless,  indigestible,  and  expensive.  Upon  the  whole  I  am  of  the 
opinion  that  the  "breads  for  diabetics"  have  profited  the  bakers, 
but  injured  the  diabetics. 

I  would  advise  physicians  to  allow  their  diabetic  patients,  except 
during  periods  of  rigid  restriction  of  diet,  daily  a  fixed  amount  of 
the  kind  of  ordinary  bread  that  they  prefer.  It  is  only  important 
to  limit  the  daily  allowance  either  by  weighing  it  every  morning  or 
by  buying  it  in  some  customary  form  containing  practically  a  fixed 
and  definite  quantity.  If  the  measurement  of  the  quantity  is  left  to 
the  patient's  eye,  it  will  not  be  long  before  the  urine  will  show  that 
he  has  taken  far  too  much  of  it. 

Graham  bread  tastes  well,  but  contains  about  forty  per  cent,  of  starch. 
Bran-bread,  a  la  Prout  or  Camplin,  tastes  badly,  otherwise  it  contains  too 
little  bran  and  too  much  starch.  Bread  may  be  baked  from  inulin,  a  substance 
found  in  the  roots  of  certain  Compositae  (inula,  taraxacum,  dahlia,  etc.). 
This  bread,  producing  levulose  and  not  glucose,  causes  much  less  glycosuria 
than  starch,  but  it  has  a  poor  taste.  Soya-bread,  from  the  Japanese  Soya  his- 
pida,  demands  twenty  per  cent,  of  starch  to  render  its  taste  at  all  pleasant. 
Dika-bread,  made  from  owala-seeds  or  the  fruits  of  the  African  Peiitaclethra 
macrophylla  (30.5  per  cent,  proteids  and  45.18  per  cent,  of  fat),  is  still  unknown 


TREATMENT.  2/5 

to  me,  but  does  not  seem  to  have  made  much  progress  as  a  food  for  diabetics. 
The  meat-bread oi  Baron  Liihdorf  contains  much  starch.  In  describing  its  taste 
as  pleasant,  the  Baron  does  so  without  frenzied  protests,  only  by  virtue  of  the 
proverb  "  de  gustibus  non  est  disputandum."  Genuine  gluten-bread  is  per- 
fectly tasteless ;  what  is  called  gluten-bread  generally  contains  three-fourths 
as  much  starch  as  an  equal  weight  of  ordinary  white  bread.  As  to  "  florador," 
"  semolina,"  and  other  preparations  of  like  kind,  they  differ  from  ordinary 
bread  chiefly  in  their  price. 

So  far  as  I  know,  there  are,  among  the  enormous  number  of  "  breads  for 
diabetics"  at  present,  only  two  of  those  mentioned  that  really  deserve  the 
attention  of  physicians — viz.,  Pavy-Seegen's  almond-bread,  and  Hundhausen's 
aleuronat  bread.  I  sometimes,  as  already  mentioned,  during  periods  of  rigid 
diet  make  use  of  almond-bread,  which,  prepared  in  the  proper  manner,  contains 
only  insignificant  quantities  of  carbohydrates.  On  boiling  with  the  addition  of 
a  few  drops  of  acetic  acid  to  the  water,  the  greater  part  of  the  nine  per  cent,  of 
sugar  and  dextrin  is  removed,  and  twenty-four  per  cent,  of  emulsin  and  fifty- 
four  per  cent,  of  fat  are  left.  For  the  market,  however,  the  bread  is  often  baked 
with  the  addition  of  some  flour  to  give  better  consistency.  It  is  not  easy  to 
digest ;  it  is  expensive  ;  and  it  has  a  dry,  unsatisfactory  taste ;  but  it  is  capable 
of  serving  the  purpose  already  mentioned.  Aleuronat  consists  chiefly  of  vege- 
table proteids.  Hundhausen's  preparation  contains  about  eighty  per  cent,  of 
that  substance,  8.7  per  cent,  of  water,  and  eight  per  cent,  of  carbohydrate.  By 
mixing  it  with  wheat-flour  one  may  produce  a  bread  that  contains  less  starch 
than  ordinary  bread,  and  that  tastes  the  better  the  more  wheat-flour  it  contains. 
If  Hundhausen's  aleuronat  flour  is  mixed  with  an  equal  weight  of  wheat-flour 
(the  minimum  amount  of  the  latter  necessary  to  make  a  fairly  pleasant  tasting 
bread),  the  whole  mixed  dry  meal  contains  45.1  per  cent,  of  proteids,  41.35  per 
cent,  of  carbohydrate,  and  11.05  P^r  cent,  of  water.  The  bread  will  thus  con- 
tain nearly  as  much  carbohydrate  as  it  does  proteid ;  it  tastes  much  less  well 
and  is  much  more  expensive  than  ordinary  bread.  Its  merit  is  that  it  contains 
less  carbohydrate  than  ordinary  bread — not  that  it  contains  vegetable  proteid, 
which  tastes  less  well,  and  is  much  less  digestible  than  animal  proteid,  as  it 
leaves  as  much  as  twenty-five  per  cent,  undigested  in  the  feces.  Ebstein 
recommends  the  unmixed  aleuronat  flour  for  sauces  and  for  the  grilling  of 
meat ;  about  twice  as  much  of  it  is  taken  for  these  purposes  as  of  wheat-flour. 

It  is  not  to  be  denied  that  a  diabetic  patient  may  derive  some  advantage 
from  using  bread  made  of  as  much  of  aleuronat  and  as  little  of  wheat-flour  as 
will  do  for  him  in  the  long  run,  thus  obtaining  a  larger  amount  of  bread,  as 
compared  to  its  quantity  of  starch,  as  a  vehicle  for  cheese  and  butter.  Even 
aleuronat  bread,  in  some  respects  the  best  of  all  "  breads  for  diabetics,"  has  the 
one  merit  common  to  them  all — i.  e.,  it  is  not  absolutely  necessary.  If  the 
physician  wishes  to  prescribe  this  special  bread,  he  had  better  have  his  patient 
buy  Hundhausen's  original  aleuronat,  and  bake  the  bread  at  home.  This  is  the 
only  easy  way  of  ascertaining  its  percentage  of  carbohydrate. 

Diabetics,  like  other  persons,  know  better  what  they  want  in  the 
way  of  food  than  with  regard  to  anything  else.     They  almost  all 


2/6  DIABETES    MELLITUS    AND    GLYCOSURIA. 

want  not  only  bread,  but  also  potatoes.  Now,  there  are  many  things 
that  contain  more  starch  than  potatoes ;  but  the  cooked  potatoes 
containing  at  the  least  fifteen  per  cent,  of  starch  and  little  besides 
but  water,  we  ought  to  persuade  our  diabetic  patients  to  do  without 
it,  as  our  ancestors  had  to  do  a  couple  of  hundred  years  ago.  When 
the  power  of  assimilation  is  active,  or  when  a  certain  amount  of 
hyperglycemia  may  be  tolerated,  we  may  allow  a  small  quantity  of 
potatoes,  always  insisting  upon  the  amount  being  weighed,  and  upon 
their  being  used  as  a  vehicle  for  butter,  in  which  capacity  they  fulfil 
a  most  useful  purpose. 

Attempts  to  find  a  substitute  for  potatoes  have  not  been  much 
more  successful  than  those  to  find  a  substitute  for  bread.  The 
tubers  of  Heliantlms  t7iberosus  L.,  the  Jerusalem  artichokes,  by 
reason  of  the  fact  that  they  contain,  when  fully  developed,*  very 
Httle  starch  or  glucose,  but  chiefly  inulin  and  levulose,  give  rise  in 
diabetes  to  a  comparatively  slight  glycosuria,  and  the  plants  are  not 
rare  in  kitchen-gardens  even  as  far  north  as  Stockholm,  and  over 
the  greater  part  of  Europe.  Jerusalem  artichokes  are,  to  my  taste, 
far  inferior  to  potatoes,  but  they  are  certainly  of  some  value  to  dia- 
betics, and,  like  potatoes,  they  constitute  a  good  vehicle  for  butter. 
The  tzibers  of  Stachys  affinis  are  chemically  similar  to  Jerusalem  arti- 
chokes ;  but,  at  least  in  my  country,  they  are  quite  small,  and  offer 
no  advantages  over  the  latter  vegetables. 

With  a  more  liberal  diet  one  may  give  those  vegetables  that  contain 
only  a  small  amount  of  starch,  but  which  contribute  largely  to 
the  necessary  variety  and  to  the  maintenance  of  the  appetite.  From 
the  list  at  the  end  of  this  book  it  will  be  found  that  we  have  chiefly 
to  keep  to  lettuce,  sphiach,  cucumbers,  young  string-beans,  celery, 
asparagus,  radishes,  mushrooms.  Tomatoes,  the  different  kinds  of 
cabbage,  almonds,  and  nuts,^  and  some  fruits  {cranberries,  straivber- 
ries)  may  often  be  allowed  in  small  quantities.  "  Sauerkraut''  has 
already  been  mentioned  as  almost  always  admissable  when  well 
fermented — unfortunately,  many  patients,  after  a  short  period  of 
warm  appreciation,  acquire  a  loathing  for  it.    We  almost  constantly 


*  When  younger,  the  tubers  contain  a  considerable  amount  of  starch  and  glucose, 
f  Hazelnuts,    walnuts,   peanuts,   Brazilian   nuts,  cocoanuts,  are  permitted,  but    not 
chestnuts. 


TREATMENT.  2// 

exclude  everything  containing  more  than  eight  per  cent,  of  carbo- 
hydrate, except  bread  and  potatoes,  which  must  be  weighed.  Some- 
times, however,  we  allow  a  large  baked  apple  at  breakfast  for  the 
sake  of  its  aperient  quality. 

Of  liquids,  tea  and  coffee  with  saccharin  or  crystallose  (see  below) 
or  levulose,  or  without  any  corrective  at  all,  are  permitted  during  the 
earlier  part  of  the  day  except  during  periods  of  severe  diet.  A  cup 
of  tea  of  ordinary  size  contains  about  one  gram,  a  cup  of  coffee  about 
two  grams,  of  carbohydrate.  I  constantly  interdict  the  use  of  both 
of  these  in  the  evening  on  account  of  their  disturbing  influence  on 
sleep,  which  is,  at  best,  not  very  sound  in  diabetic  patients.  A 
glass  of  milk,  or  some  alkahne  water,  or  even  a  weak  grog  is  a  better 
ingredient  of  the  patient's  supper  or  late  dinner. 

Moderate  quantities  of  red  wines,  European  or  American,  may 
be  allowed  ;  of  white  wines  those  from  the  Rhine  are  the  best. 

Among  alcoholic  Hquors,  however,  none  is  better  for  the  dia- 
betic patient  than  cognac,  brandy,  whisky,  gin,  and  similar  drinks. 
These  must  be  taken  diluted,  best  with  some  carbonated  mineral 
water,  and  the  amount  of  alcohol  they  contain  must  not  in  the 
twenty-four  hours  exceed  one-fourth,  at  the  very  utmost  one-half, 
of  a  gram  per  kilo  of  bodily  weight. 

All  sweet  wines, — champagne,  port,  Madeira,  sherry,  marsala, 
etc., — "  liqueurs,"  and  punches  are  forbidden  under  all  circum- 
stances in  cases  of  diabetes. 

It  is  also  well  to  interdict  absolutely  porter,  beer,  and  ales  of  all 
kinds.  These  contain  a  good  deal  of  carbohydrates,  are  generally 
drunk  in  considerable  quantities,  if  drunk  at  all,  and  are  easily 
dispensed  with. 

The  usefulness  of  milk  *  for  the  diabetic  patient  is  more  difficult 
to  decide,  and  to   some  extent  is  a  matter  of  individuality.     Milk 

*  Some  physicians  forbid  milk  in  all  cases  of  diabetes — a  position  that  may  possibly 
be  defended.  Dr.  Donkin  has  been  unfortunate  enough  to  recommend  it  skimmed  as  an 
exclusive  food  in  cases  of  diabetes.  This  prescription  can  not  possibly  be  defended,  even 
if  it  did  not  include  the  skimming,  which  deprives  the  diabetic  of  a  large  part  of  the  fat 
and  leaves  the  carbohydrate.  I  have  myself  never  prescribed  the  "  Donkin  cure,"  but  I 
have  several  times  seen  it  prescribed  by  others,  with  its  necessarily  signally  bad  results. 
An  adult  person  requires  about  six  liters  of  skimmed  milk  in  order  to  secure  the  necessary 
amount  of  calories.  This  gives  him  nearly  three  hundred  grams  of  lactose,  and  does 
not,  in  other  respects,  constitute  the  best  kind  of  diet. 


2"]%  DIABETES    MELLITUS    AND    GLYCOSURIA. 

contains  nearly  five  per  cent,  of  lactose,  and  can  not  be  allowed  at 
all  during  periods  of  rigid  restriction  of  the  diet ;  it  ought  never  to 
be  allowed  in  large  or  unlimited  quantities  in  any  case  of  diabetes. 
In  all  severe  cases,  however,  and  in  many  mild  cases  one  may  allow 
200  or  300  cu.  cm.  of  unskimmed  milk  to  be  taken  at  supper. 
The  sour  milk,  much  in  use  during  the  summer  in  the  north  of 
Europe,  in  which  the  lactose  is  in  large  part  changed  into  lactic  acid, 
forms  a  most  pleasant,  wholesome,  and  popular  article  of  food  for 
the  diabetic  patient.  At  present  there  are  other  methods  of  remov- 
ing the  greater  part  of  the  lactose  from  the  milk  ;  when  this  can 
be  done,  the  greatest  objection  to  the  use  of  milk  in  cases  of  diabe- 
tes (not  belonging  to  the  class  of  persons  in  whom  dyspeptic  symp- 
toms arise  in  consequence)  is  removed. 

Diabetic  patients  often  are  very  thirsty  and  consume  considerable 
quantities  of  drinking  water.  This  is  partly  a  result  of  the  increased 
amount  of  sugar  and  of  toxins  in  the  blood,  of  nature's  attempt  to 
eliminate  these  toxins  as  far  as  possible,  and  of  the  difficulty  in 
providing  the  tissues  with  the  necessary  supply  of  water  from  the 
strongly  sacchariferous  blood.  There  is  nothing  so  absurd  that  it 
can  not  be  prescribed,  and  there  are  physicians  who  advise  their 
diabetic  patients  to  restrict  themselves  in  the  drinking  of  water.  If 
this  is  done  at  all  extravagantly,  it  tortures  the  patient,  increases  the 
diabetic  and  other  deleterious  substances  in  the  blood,  changes  the 
working  conditions  of  the  heart,  increases  the  dangers  from  too  con- 
centrated secretions  (gall-stones,  urinary  concretions,  etc.),  acts 
unfavorably  on  the  nervous  system,  and  in  severe  cases  multiplies 
the  danger  of  coma.  The  drawbacks  of  polydipsia  are  the  disten- 
tion of  the  stomach  and  the  increase  in  the  work  of  the  heart. 
Both  of  these  effects  are  greatly  diminished  by  the  avoidance  on  the 
part  of  the  patient  of  drinking  large  quantities  at  once.  Diabetic 
patients  should  be  advised  to  drink  as  much  water  as  they  like 
during  the  twenty-four  hours,  but  to  take  the  whole  quantity  in 
frequent  small  portions.  Instead  of  ordinary  water  they  may  with 
advantage  sometimes  drink  carbonated  alkaline  mineral  waters.  If 
the  polydipsia  is  very  marked,  the  patient  may  be  spared  a  couple 
of  hundred  calories  by  heating  the  drinking  water. 

Different  substances  on  account  of  their  sweet  taste  have  lately 
been  used  as  substitutes  for  suear  in  cases  of  diabetes.      The  most 


TREATMENT.  2/9 

common  of  these  is  (Fahlberg's)  saccharin  (=anhydro-ortho-sulph- 
amin-benzoic  acid).  This  substance,  taken  in  amounts  of  a  few 
centigrams  every  day,  in  the  form  of  the  small  tablets  to  be  had  of 
druggists,  sweetens  tea  and  coffee  or  anything  else  with  which  it  is 
used.  I  am  not  certain  that  I  have  ever  observed  the  dyspeptic 
effects  dwelt  upon  by  Bernstein,  v.  Jaksch,  and  others.  Small 
amounts  seem  harmless  in  this  respect.  The  use  of  saccharin, 
however,  causes  the  appearance  of  a  reducing  substance  in  the 
urine,  and  from  this  fact  alone  some  influence  on  the  kidneys  might 
be  suspected.  The  taste  of  saccharin  is  not  pleasant,  neither  is  the 
use  of  a  sweetening  substance  very  important  to  the  patient ;  most 
persons  become  indifferent  in  this  respect.  The  antizymotic  quality 
of  saccharin  is  too  weak  to  give  it  any  distinct  advantage  in  ordi- 
nary small  amounts.  I  usually  tell  patients  of  saccharin  and 
advise  them  to  take  as  few  tablets  as  possible  daily  ;  they  then  gen- 
erally use  it  for  a  time,  and  then  without  regret  abandon  it.  Sticrol 
or  diilciii  (=paraphenetol-carbamin)  is  in  large  doses  a  poison 
(Kossel,  Aldehoff).  I  have  not  used  it,  though  several  writers 
affirm  that  they  have  seen  no  bad  effects  from  small  amounts.  I  do 
not  know  of  crystallose  more  than  its  appearance  and  its  taste,  which 
latter  is  more  pleasant  than  that  of  saccharin.  Mannite  causes 
diarrhea. 

Levidose  has  distinct  nutritive  value,  increases  the  glycosuria 
but  moderately,  and  has  no  other  bad  effects.  It  is,  however,  still 
too  expensive  for  poor  patients,  and  some  persons  take  a  dislike  to 
it. 

An  enormous  and  a  significant  number  of  "specific  "  and  other 
remedies  have  been  used  in  the  treatment  of  diabetes.  Upon  the 
whole,  too  much  importance  has  been  attached  to  any  diminution 
in  the  hyperglycemia  and  glycosuria,  however  transitory,  and 
too  little  consideration  has  been  given  to  the  first  duty  of  every 
physician — viz.,  not  to  do  harm.  It  seems  almost  incredible  that 
there  are  physicians  who  recommend,  e.  g.,  uranium  nitrate  for  the 
purpose  of  decreasing  the  glycosuria,  and  it  seems  certain  that  even 
minimum  quantities  of  this  poison  with  its  violently  irritating 
effects  on  the  alimentary  canal  and  on  the  kidneys  must  in  the 
course  of  an  hour  do  more  harm  than  considerable  hyperglycemia 


2 So  DIABETES    MELLITUS    AND    GLYCOSURIA. 

will  in  the  course  of  a  week.  The  "specific"  influence  of  many 
drugs  may  probably  be  only  imaginary,  and  the  diminution  of 
hyperglycemia  and  glycosuria  a  result  of  impaired  digestion.  Even 
if  this  "  specific  "  influence  is  real,  its  cost  may  easily  be  too  great, 
and  I  believe  it  to  be  good  advice  to  recommend  the  administration 
to  diabetic  patients  of  only  such  drugs  as  can  certainly  be  taken  for 
some  time  without  serious  detriment.  Even  the  best  "specific" 
remedies  for  diabetes  are  but  very  uncertain  and  weak  in  any 
"  specific  "  influence,  and  the  longer  one  has  the  opportunity  of 
watching  the  effects  of  extolled  remedies  of  this  kind,  the  more 
skeptical  does  he  become  of  their  great  value. 

Of  some  real,  though  not  of  great,  specific  value  is  opitan,  which 
has  been  used  in  the  treatment  of  diabetes  at  least  since  the  begin- 
ning of  the  nineteenth  century.  In  many  cases — but  not  in  all — it 
distinctly  diminishes  the  glycosuria  and,  what  I  consider  to  be  much 
more  important,  it  improves  the  patient's  general  somatic  and  mental 
state.  I  prescribe  it  when  I  find  a  rapid  diminution  in  the  power 
of  assimilation  and  during  periods  of  nervous  exacerbations  ;  under 
the  latter  condition  it  is  really  of  decided  value.  One  begins  with 
small  doses,  increases  them  to  quite  considerable  ones  (from  8  to  lo 
centigrams — ly^  io  ly^  grains — of  pure  opium  per  day  for  an 
adult),  and  after  some  time,  perhaps  days  or  weeks,  gradually 
diminishes  the  dose,  and  finally  withdraws  the  drug  altogether.  It 
is  advisable  never  to  use  opium  for  any  great  length  of  time. 

As  to  codein,  and  still  more  as  to  niorpliin,  these  are  in  every  re- 
spect much  less  valuable  in  cases  of  diabetes  than  is  opium.  Con- 
sidering the  great  danger  to  the  patient  of  becoming  addicted  to 
them  from  the  prolonged  daily  use  of  any  of  these  remedies, — cer- 
tainly one  of  the  worst  of  human  miseries, — I  think  it  the  physician's 
bounden  duty,  under  all  conditions,  to  reserve  them  for  the  mitiga- 
tion of  transitory,  severe  pains  or  of  perfectly  hopeless  conditions. 

When  coma  is  present  or  there  is  imminent  danger  thereof,  the 
administration  of  narcotic  or  hypnotic  remedies  is  avoided  as  much 
as  possible. 

Next  to  opium,  arsenic  may,  perhaps,  be  mentioned  as  having  some 
specific  value  in  the  treatment  of  diabetes.  In  some  cases  it  does 
somewhat,  though  never  to  any  large  extent,  cause  a  diminution  in 
the  glycosuria  ;  it  may,  perhaps,  counteract  the  conversion  of  glyco- 


TREATMENT.  28 1 

gen  into  glucose  and  favor  its  transformation  into  fat  in  the  liver, 
where,  as  has  been  mentioned,  it  in  some  way  causes  a  diminution 
in  the  glycogen.  It  is,  besides,  as  is  well  known,  a  splendid  tonic, 
and  in  diabetic  patients  who  are  also  anemic  it  may  be  given  with 
great  advantage.  In  my  opinion  one  had  better  adhere  to  small 
doses,  beginning  with  one  and  slowly  increasing  to  three  or  four 
drops  of  Fowler's  solution  thrice  daily,  after  meals,  or  giving  a 
corresponding  amount  of  arsenic  in  pills  (from  gr.  yi^  to  gr.  ^). 
After  a  couple  of  weeks  the  dose  is  slowly  diminished.  One  may, 
in  cases  of  diabetes,  often  with  advantage  combine  arsenic  with 
opium. 

The  alkaline  salts,  especially  sodium  bicarbonate,  have  been 
used  in  the  treatment  of  diabetes  for  at  least  since  the  time  of 
Willis  in  the  seventeenth  century.  They  are  believed  to  diminish 
the  glycosuria,  either  by  increasing  the  combustion  of  sugar  in  the 
tissues  or  by  facilitating  the  storage  of  glycogen  and  counteracting 
the  formation  of  glucose  in  the  liver.  The  alkaline  salts  have  dif- 
ferent merits  (see  below) ;  but  their  power  of  diminishing  glycosuria 
is  exceedingly  slight,  and,  unless  large  doses  are  given,  conscien- 
tious investigation  often  fails  to  discern  any  decrease  in  the  amount 
of  sugar  excreted  in  the  urine.  Mialhe  administered  twenty  grams 
of  sodium  bicarbonate  a  day,  with  the  effect  of  diminishing  the 
glycosuria  somewhat ;  but  such  doses  give  rise  to  gastrointestinal 
disorders  and  weaken  the  patient.  Richardiere  gives  it  in  doses  of 
from  four  to  ten  grams  a  day  for  months  ;  but  only  periodically, 
and  never  in  cases  of  pancreatic  diabetes  or  in  any  case  complicated 
by  tuberculosis  or  by  marasmus.  Sodium  bicarbonate  is  given 
chiefly  in  mineral  waters,  and  then  only  in  doses  of  a  few  grams 
a  day,  and  the  enormous  doses  are  used  by  most  physicians  only 
in  the  presence  of  coma,  or  when  there  is  manifest  danger  of  it. 
The  salts  of  tartaric,  citric,  phosphoric,  lactic,  benzoic,  salicylic,  hip- 
puric,  and  boric  acids  are  also  used,  though  far  less  than  sodium 
bicarbonate. 

Aminonia,  especially  as  carbonate  and  citrate,  is  also  used,  and 
has  the  merit  of  stimulating  and  of  increasing  the  perspiration. 
Bouchardat  recommends  potassium  carbonate  and  sodium  and  potas- 
sium tartrate  for  their  powerful  effect  in  eliminating  uric  acid. 
Clemens'  solution  contains  potassium  carbonate,  arsenic,  and  bromids. 
19 


282  DIABETES    MELLITUS    AND    GLYCOSURIA. 

Calcmni  is  for  the  moment  and  in  some  places  popular  in  the 
treatment  of  diabetes.  Grube  gives  his  patients,  four  times  a  day,  at 
meals,  large  doses  of  a  mixture  of  seven  parts  of  calciiivi  carbonate 
and  one  part  o{  calcium  phosphate.  These  salts  do  not  influence  the 
glycosuria,  but  they  are  said  to  improve  the  general  state  and  to 
facilitate  the  ingestion  of  fat.  Robin  uses  calci?iin  phosphate  and 
glycerin.  Those  who  give  their  diabetic  patients  large  quantities  of 
milk  often  add  calcium  carbonate.  Magnesium  hydrato-carbonate 
and  calcined  magnesia  are  also  used,  especially  in  cases  with  hyper- 
acidity of  the  stomach  and  constipation.  Viau-Grand-Marais  recom- 
mends strontium  bromid ;  Martineau  gives  litlmim  carbonate  (with 
arsenic). 

The  alkaline  and  alkaline-saline  spas  are  visited  by  large  numbers  of  dia- 
betics. Carlsbad,  Vichy,  and  Neuenahr  enjoy  at  present  the  greatest  repu- 
tation for  their  beneficial  influence  on  diabetes.  As  a  student  of  diabetes  and 
as  a  practising  physician  in  Carlsbad  I  have  made  it  my  purpose  to  acquire  as 
correct  an  idea  as  possible  of  what  may  be  reasonably  expected  for  a  diabetic 
patient  from  a  sojourn  of  some  weeks  at  one  of  these  health-resorts.  I  consider 
it  as  great  an  advantage  for  these  resorts  as  for  the  medical  profession  and  for 
the  patients  that  no  false  pretensions  are  supported  and  consequently  no  dis- 
appointments incurred,  and  that,  on  the  other  hand,  the  knowledge  of  the  good 
results  that  undeniably  are  in  many  cases  to  be  obtained  is  spread  as  far  as 
possible. 

As  for  the  glycosuria,  Carlsbad  and  Vichy  water,  and  doubtless,  also,  Neuen- 
ahr water  in  the  moderate  and  rational  amounts  recommended  at  present, 
which  scarcely  ever  go  beyond  a  liter  a  day,  have  no  appreciable  influence,  or 
one  that  is  extremely  slight  and  uncertain.* 

Does  this  mean  that  a  course  of  treatment  at  Carlsbad,  Vichy,  or  Neuenahr 
has  no  value  at  all  for  diabetic  patients  ?  By  no  means.  I  feel  safe  in  saying 
that  most  diabetic  patients,  especially  in  the  mild  stage,  whom  I  or  others 
have  had  occasion  to  observe  in  Carlsbad,  have  derived  as  considerable  a 


*  I  protest,  a  priori,  against  any  denial  of  this  fact  not  founded  on  pure  experimentation. 
I  pass  entirely  over  the  naive  reports  on  the  influence  of  mineral  waters  on  the  glycosuria 
resulting  from  a  simultaneous  restriction  of  carbohydrates — they  are  not  worth  discussing. 
Neither  will  it  do  first  to  determine  the  supply  of  carbohydrate,  and  the  amount  of  glucose 
excreted  with  the  patient  at  home  and  occupied  with  his  daily  work,  with  its  strains  and 
emotions,  and  then  to  make  the  same  determinations  at  the  spa  with  the  patient  at  leisure 
and  subjected  to  the  effect  of  other  therapeutic  agents  than  the  mineral  water.  The 
experiment  requires  exact  determinations  of  carbohydrate  and  glycosuria  during  two  not 
too  short  periods,  the  one  with  and  the  other  without  mineral  water,  but  both  otherwise 
under  as  nearly  similar  circumstances  as  possible.  Any  one  that  undertakes  the  consider- 
able amount  of  work  required  in  such   an  experiment  will    find  that  the  glycosuria, 


TREATMENT.  283 

benefit  from  their  sojourn  there  as  might  be  expected  by  any  reasonable  person. 
[We  know  that  most  laymen,  and  even  some  physicians,  are  not  reasonable.] 
I  do  not  consider  the  mineral  water  at  Carlsbad,  excellent  as  it  is,  to  be  the 
only  or  even  the  first  therapeutic  resource  of  the  place.  Still,  the  water  has  a 
good  influence  on  dyspeptic  symptoms,  which  are  common  in  diabetic  patients, 
as  they  are  in  others  ;  it  also  has  a  good  influence  on  the  constipation,  which  is 
equally  common.  It  increases  some  of  the  secretions, — diabetic  patients  are, 
during  its  use,  often  less  troubled  by  dryness  of  the  mouth, — and  I  believe  that  this 
influence  on  the  bile  is  of  benefit  in  many  cases.  I  am  also  willing  to  acknowl- 
edge the  probability  of  some  beneficial  influence  on  the  liver  in  other  respects, 
and  that  an  enlarged  and  tender  liver  becomes  sometimes,  under  the  use  of 
the  mineral  water,  smaller  and  less  sensitive  to  pressure.  Finally,  I  will  not 
deny  a  favorable  influence  on  gouty  symptoms,  which  are  very  common  in 
diabetics  of  the  florid  type  in  the  mild  stage  of  the  dystrophy.  The  alkaline 
water  must  also  have  some  slight  neutralizing  effect  on  the  acidosis  in  the 
severe  stage,  though,  according  to  my  opinion,  only  a  comparatively  small 
number  of  patients  in  this  stage  do  well  in  undertaking  a  journey  of  any  length. 
It  is,  fortunately,  not  necessary  to  enter  here  into  details  with  regard  to  the 
influence  of  the  mineral  water  on  the  metabolic  processes ;  but  if  it  accom- 
plishes only  what  I  have  already  acknowledged,  it  is  well  worth  the  drinking. 

The  patient's  absence  from  home  and  its  cares,  his  rest  from  intellectual 
work  and  mental  worry,  the  hygienic  and  dietetic  discipline,  so  much  more 
easily  enforced  in  a  health-resort  than  anywhere  else,  and  the  other  therapeu- 
tic resources  available  in  such  a  place,  are,  in  my  opinion,  together  of  much 
greater  value  than  any  mineral  water,  and  it  is  these  considerations  that  make 
up  the  enormous  difference  between  a  "  cure  "  at  home  and  the  "  cure  "  at  a 
watering-place.  The  water,  as  it  bubbles  from  the  springs,  or  is  contained  in 
well-corked  and  well-preserved  bottles,  is,  as  every  sensible  person  can  under- 
stand, exactly  the  same. 

As  I  attach  less  importance  to  local  mineral  water  than  to  other  therapeutic 
agents,  it  is  evident  that  in  my  choice  between  different  health-resorts  I  shall 
be  influenced  less  by  the  mineral  water  itself  than  by  other  circumstances,  some 
of  an  individual  and  some  of  a  local  nature. 

There  is,  unfortunately,  a  single  feature  common  to  almost  all  advice  in  this 
respect  recorded  in   the   literature — viz.,  one   always   finds  that  the  adviser 


cceteris  paribus,  with  or  without  the  use  of  mineral  water,  remains  the  same,  or  that  the 
variations  are  no  greater  than  they  are  without  any  appreciable  external  change  whatever. 
Even  in  cases  of  simple  glycosuria  one  finds  with  the  use  daily  of  a  liter  of  mineral  water 
that  a  faint  trace  of  sugar,  just  large  enough  to  cause  a  distinct  reaction,  remains  as  it 
showed  itself  before  the  use  of  the  mineral  water.  In  the  different  stages  of  diabetes  one 
will  arrive  at  the  same  results,  though  there  may  often  remain  some  doubt  as  to  the  cause 
of  small  variations  in  the  excretion  sometimes  observed  even  under  apparently  perfectly 
similar  circumstances.  This  will  be  the  case  whether  the  mineral  water  is  di-unk  imme- 
diately at  the  springs  or  from  bottles ;  if  it  were  not,  who  would  undertake  to  explain 
reasonably  any  possible  difference?  Kiilz's  and  all  other  serious  investigations  on  this 
subject  have  led  to  the  same  results  as  my  own. 


284  DIABETES    MELLITUS    AND    GLYCOSURIA. 

recommends,  with  rare  exceptions,  the  sending  of  patients  to  the  health-resort 
in  which  he  is  personally  interested  and  is  engaged  in  practice.  The  late  Dr. 
Schmitz,  who  practised  in  Neuenahr,  stated  that,  in  order  to  avoid  debilitating 
the  organism,  patients  had  better  be  sent  to  Neuenahr  rather  than  to  Carls- 
bad, whose  waters,  according  to  Schmitz,  contain  rather  large  amounts  of 
sodium  sulphate  ;  or  to  Vichy,  where  waters  were  said  to  contain  rather  large 
amounts  of  sodium  bicarbonate.  As  it  is  always  advantageous  not  to  debili- 
tate the  organism,  these  statements  seem  to  mean  that  one  must  never  send 
patients  to  Carlsbad  or  Vichy,  but  always  to  Neuenahr — and  presumably  (as 
long  as  he  lived)  to  Dr.  Schmitz.  The  French  have  no  great  regard  either  for 
Neuenahr  or  for  Carlsbad,  which  latter  place  they,  by  the  way,  often  believe  to 
belong  to  Germany.  "  II  n'y  a  lieu  d'  essayer  Carlsbad  que  dans  les  cas  ou 
une  au  deux  cures  a  Vichy  n'auraient  pas  donne  de  resultats  satisfaisants." 
The  physicians  of  Carlsbad,  on  the  other  hand,  think  Vichy  good  only  for 
amusement,  and  smile  at  mention  of  the  0.77  gram  of  bicarbonate  which  is 
the  essential  ingredient  in  a  liter  of  the  "  Augustenquelle  "  in  Neuenahr,  and 
affirm  that  this  latter  place  is  dangerous  for  visitors  on  account  of  the  risk 
of  death  from  "the  blues,"  and  that  their  own  place,  in  point  of  therapeutic 
resources  of  all  kinds,  is  the  first  health-resort  that  is,  or  was,  or  ever  will  be. 

I  do  not  intend  to  offer  like  recommendations.  I  find  it  a  difficult  task  to 
decide  which  of  these  superstitions  is  the  sillier  :  the  one  that  ascribes  such  a 
debilitating  effect  to  the  small  quantities  of  alkaline  sulphates,  carbonates,  and 
chlorids  in  Carlsbad,*  or  the  one  that  attributes  such  wonderful  effects  to  those 
salts  or  to  the  sodium  bicarbonate  at  Vichy  or  Neuenahr  ;  and  I  am  willing  at 
once  to  acknowledge  that  many  diabetic  patients  can  derive  benefits  from  a 
"  cure  "  at  any  one  of  the  three  places  named.  I  would,  however,  advise 
against  sending  thither  patients  in  constant  danger  of  coma,  or  suffering  from 
tuberculosis,  marasmus,  or  advanced  arteriosclerosis,  organic  heart  disease,  or 
extreme  senility.  Fully  developed  mental  disease  also  constitutes  a  contra- 
indication. 

The  seeds  of  the  Indian  plant  Syzyghun  jambulanwn  really  in 
many  cases  diminish  glycosuria ;  in  other  cases  they  seem  not  to 
have  the  slightest  influence  in  that  direction,  whether  the  fluid  ex- 
tract or  the  powdered  seeds  are  used.  Lewaschew  administered 
from  fifteen  to  thirty  grams  of  the  powdered  seeds.  I  generally 
have  given  no  more  than  ten  grams,  and  have  not  observed  any  dys- 
peptic or  other  detrimental  results.  Fichtner  saw  the  glycosuria 
increase  after  the  use  of  the  drug.  Lepine  and  Barral  believe  that 
it  increases  both  the  production  and  the  consumption  of  glucose. 


*  The  notion  existing  among  laymen  and,  in  some  degree,  also  among  physicians  of 
the  debilitating  influence  of  a  course  of  treatment  at  Carlsbad  owes  its  origin  to  the 
absurd  system  prevailing  several  decades  ago  in  this  Bohemian  watering-place  of  giving 
patients  enormous  doses  of  the  mineral  water  and  of  starving  them  half  to  death. 


TREATMENT.  285 

Weil  introduced  the  leaves  of  Vacciniuin  myrtillus  L.  (blue- 
berries) in  the  therapeutics  of  diabetes.  The  twigs,  with  the  young 
leaves,  are  collected  early  in  summer,  when  the  bushes  are  in 
bloom.  An  infusion  certainly  causes  diminution  in  the  glycosuria ; 
but  at  the  same  time  it  causes  distinct  dyspeptic  disturbances.  I 
have  also  heard  patients  complain  of  dyspeptic  derangement  after 
the  use  of  Jasper's  pilulae  myrtilli,  and  I  have  of  late  entirely  ceased 
to  use  preparations  of  Vaccinuun  myrtilliis  L. 

Antifebrm,  antipyrin,  phenacetin,  and  exalgin  have  been  recom- 
mended by  French  and  other  writers  as  "  specifics  "  in  cases  of  dia- 
betes. I  should  not  prescribe  any  of  these  substances  for  any  length 
of  time.  For  the  sake  of  the  experiment,  however,  I  gave  one  of 
my  patients  with  an  unvarying  amount  of  glucose  in  the  urine 
phenacetin  at  different  times,  and  always  with  a  distinct  increase  in 
the  glycosuria.  Lepine  and  Barral  believe  that  antipyrin  dimin- 
ishes both  the  production  and  the  consumption  of  sugar.  Even 
though  it  causes  diminution  in  the  glycosuria  in  cases  in  which 
there  is  increased  production  of  glucose  in  the  liver,  I  consider  the 
patients  better  off  without  antipyrin  or  related  substances. 

Quinin  was  used  by  Dobson  more  than  a  hundred  years  ago,  and 
it  is  still  recommended  as  a  "specific"  by  Worms  and  others.  It 
undoubtedly  has  a  good  influence  in  cases  of  glycosuria  or  diabetes 
due  to  malaria,  of  which  several  reliable  instances  have  been  placed 
on  record.  In  other  cases  of  simple  glycosuria  and  diabetes  I  have 
failed  to  observe  any  influence  on  the  excretion  of  sugar. 

The  salts  of  broniin  are  excellent  and  comparatively  innocuous 
remedies,  and  of  great  value  in  the  presence  of  some  neurasthenic 
disorders  on  account  of  their  sedative  action  ;  and  they  are  often 
used  in  the  treatment  of  diabetes.  I  have  found  it  most  advan- 
tageous to  give  them  only  once  a  day,  in  the  evening,  but  then  in 
rather  large  doses — not  less  than  two  grams.  I  prefer  sodium 
bromid  to  potassium  bromid.  Neither  the  one  nor  the  other  salt 
exhibited  any  influence  whatever  on  the  excretion  of  glucose  in  a 
number  of  cases  studied  from  this  point  of  view. 

Among  vegetable  "  nervines,"  valerian  is  the  most  recommended 
and  is  used  especially  often  in  France.  It  is  said  chiefly  to  diminish 
the  polyuria.      Bouchard  administers  ten   grams    or    more    of  the 


286  DIABETES    MELLITUS    AND    GLYCOSURIA. 

extract   per   day;   Lecoche    from    0.30  to    0.50    gram;    Dreyfus- 
Brisac  from  three  to  four  grams  with  opium. 

Cantia  agra  is  used  in  America,  but  I  know  nothing  of  its  value. 

Potassium  iodid  is  used  in  the  treatment  of  diabetes,  as  it  is  also  in  that  of 
most  other  diseases.  In  some  cases  of  diabetes  complicated  by  syphilis  I 
failed  to  observe  any  effect  upon  the  glycosuria,  even  after  the  administration 
of  large  doses. 

Sampson  recommends  potassium  perinanganate  by  the  mouth,  in  small 
doses,  especially  for  anemic  or  lymphatic  diabetics.  Some  French  physicians 
believe  that  they  have  attained  "  de  grands  succes  curatifs  "  with  this  remedy. 

Potassium  bichlorate  and  potassium  chlorate  have  also  been  used  in  the 
treatment  of  diabetes,  and  have  shown  their  uselessness  in  this  respect. 

Cantani,  earlier  in  his  career,  praised /a^/zir  acid'vsx  the  treatment  of  diabetes. 
It  causes  dyspeptic  symptoms. 

Glycerin,  introduced  in  the  fifties  by  Basham,  was  for  a  time  much  used  as 
a  nutrient,  chiefly  on  account  of  Schultzen's  theory  of  diabetes.  It  is  now 
almost  abandoned,  less  because  Kiilz  proved  that  it  somewhat  increases  the 
glycosuria  than  because  it  causes  gastro-intestinal  catarrh.  So  much  has  been 
written  on  the  subject  that  I  feel  unwilling  to  add  more.  If  any  one  should  be 
anxious  to  give  it  or  to  take  it,  he  had  better  do  so  according  to  the  following 
(French)  prescription  :  Fifty  grams  of  glycerin,  one  liter  of  water,  five  grams  of 
citric  acid  ;  to  be  drunk  in  the  course  of  the  day. 

Bouchardat  tried  and  gave  up  inhalations  of  oxygen.  Benzi  trusted  to 
ozone.  Richardson  produced  with  oxygen  hydrogen  dioxid  in  water  and  gave 
of  this  solution  one-half  ounce  three  times  a  day. 

I  must  not  omit  to  mention  the  different  ferments  that  have  been  recom- 
mended on  various  grounds  in  the  treatment  of  diabetes.  Pepsin  does  no 
harm.  Yeast  (of  beer)  would  appear  likely  to  do  so  in  some  degree,  but 
according  to  Dr.  Cassaet  its  action  is  fperfectly  marvelous,  and  the  agent 
ought  to  be  blessed  by  every  diabetic  patient.  "  Son  etat  general  se  releve, 
son  appetit  renait,  ses  forces  augment,  ses  donleurs  s'attenuent  son  poids 
enfin  se  modifie,"  which  last  means  that  the  bodily  weight  may  increase  from 
three  to  eight  kilograms  in  a  fortnight.  I  have  never  used  yeast  in  this  way, 
and  I  feel  certain  that  I  never  shall.  Lepine  saw  the  glycosuria  diminish  after 
subcutaneous  injections  oi  diastatic  ferment  {see  below). 

Robin  has  devised  a  system  of  giving  specifics.  He  begins  by  administer- 
ing antipyrin,  one  gram  twice  a  day,  for  five  days.  Even  he  considers  antipy- 
rin  contraindicated  by  anorexia,  albuminuria,  marasmus,  and  autophagy,  and 
to  be  useful  chiefly  in  mild  cases  ("  diabete  gras  ").  Then  for  a  fortnight 
he  gives  a  mixture  of  arsenic,  codein,  and  lithium  [R.  Sodii  arsenitis,  gm. 
0.002;  Lithii  carbonatis,  gm.  0.12;  Codeinge,  gm.  0.02;  Pulvis  radicis  Vale- 
rianae, gm.  0.25;  Extracti  chin,  sin.,  gm.  0.40.  One  such  powder  is  to  be 
taken  at  breakfast  and  one  at  dinner,  daily] ,  with  an  interval  of  several  days  in 
the  middle  of  this  period.  The  treatment  is  concluded  with  opium,  belladonna, 
valerian,  quinin,  bromids,  alkalies,  and  cod-liver  oil.  "  Quid  bonum  faustum- 
que  sit  populo  Gallico  !  " 


TREATMENT.  28/ 

Theobroinin  has  been  used  by  different  clinicians.  Lindner's  "  glyco- 
solvol,"  put  on  the  market  as  a  specific  in  the  treatment  of  diabetes,  consists  of 
theobromin-trypsin  oxypropionate. 

Besides  the  substances  mentioned,  the  greater  number  of  the  drugs  of  vege- 
table or  mineral  origin  found  in  the  Pharmacopeia  have  been  used  in  the 
treatment  of  diabetes.  As  I  consider  all  of  these  as  worse  than  useless,  I  shall 
only  mention  some  of  them  by  name :  Phosphorus,  iodoform,  uranium 
nitrate,  alum,  thallium  sulphate,  the  salts  of  copper,  the  mineral  acids,  carbolic 
acid,  creosote,  thymol,  benzosol,  salol,  naphtalin,  balsam  of  copaiba  or  of 
Peru,  tannic  acid,  rhatany,  catechu,  cubebs,  piperazin,  camphor,  colchicum, 
santonin,  belladonna  and  atropin,  jaborandi  leaves  and  pilocarpin,  secale  cor- 
nutum,  and  ergotin.  The  last  remedy  recommended,  so  far  as  I  know,  is 
methylene-blue  (Pierre-Marie,  Le  Goff ). 

Dismissing  this  long  list  from  mind,  we  may  devote  a  brief  con- 
sideration to  the  proper  use  of  mercury  in  cases  of  diabetes  asso- 
ciated with  syphilis.  The  diabetic  organism  is  often  more  sensitive 
than  others  to  poisons,  and  medical  literature  contains  warnings 
against  the  too  free  use  of  mercury  for  antisyphilitic  purposes  with 
diabetic  patients.  As  has  already  been  mentioned,  syphilis  has  in  rare 
cases  evidently  been  the  cause  of  the  diabetes  by  affecting  in  some 
way  the  nervous  centers.  If  any  reasons  exist  in  such  a  case  to  sus- 
pect the  presence  of  an  active  intracranial  syphilitic  process,  there  can 
be  no  doubt  as  to  the  physician's  duty  to  take  almost  any  other  risk 
than  that  of  an  undisturbed  continuation  of  the  local  syphilitic  process. 
Neither  the  modern  large  doses  of  potassium  iodid  nor  anything  else 
has  shown  itself  as  useful  an  antisyphilitic  remedy  as  mercury,  and  I 
would  not  hesitate  to  administer  it  quite  energetically  in  such  a  case 
in  the  manner  that  continues  to  be  the  best,  the  most  efficient,  and 
the  least  objectionable:  viz.,  the  old  "inunction-cure,"  Avith  the 
usual  precautions  against  mercurial  poisonmg.  I  have  been  gov- 
erned by  the  rule  to  assume  any  reasonable  risk  rather  than  to  leave 
the  organism  a  probable  prey  to  syphilis  in  any  case  in  which  there 
is  a  mere  accidental  complication  of  syphilis  and  diabetes,  whenever 
there  is  overwhelming  reason  to  fear  the  presence  of  the  first- 
named  disease.  Views  on  the  subject  of  antisyphilitic  treatment 
vary  exceedingly  even  now,  when  the  day  of  the  antimercurial 
craze  has  passed.  For  myself,  I  treated  my  syphilitic  patients  more 
or  less  a  la  Foiirnier  before  I  had  ever  read  his  work,  and  I  believe 
in  varying  its  details  in  diabetic  cases  only  according  to  the  rules 
that  we  follow  in  general.      In  my  own  cases  of  associated  syphilis 


2  88  DIABETES    MELLITUS    AND    GLYCOSURIA. 

and  diabetes  the  latter  disease  has  been  in  the  mild  stage,  and  I 
have  not  observed  any  marked  or  peculiarly  bad  effects  from  the 
inunctions. 

Since  thyroidin  has  yielded  such  good  results  in  the  treatment  of 
myxedema,  organotherapy  (though  with  much  less  good  results)  has 
been  appUed  to  numerous  other  diseases,  and  also  to  diabetes.* 
Some  physicians  simply  administer  portions  of  pancreas,  raw  or 
sHghtly  cooked.  Others  make  an  extract  of  the  raw  pancreas  of 
sheep  or  oxen,  which  is  finely  cut  and  macerated  for  twenty-four 
hours  in  its  own  weight  of  ("physiologic")  solution  of  sodium 
chlorid  or  in  glycerin  ;  this  extract  is  later  diluted  with  water.  The 
filtered  extract  is  afterward  used  in  subcutaneous  injection  (Comby, 
Lancereaux,  Gley,  Thiroloix,  Ausset  de  Cerenville,  Battistini,  etc.). 
Lepine  macerates  a  pancreas  in  one  liter  of  water,  with  one  gram  of 
sulphuric  acid  and  five  grams  of  malt-diastase,  for  two  or  three 
hours,  at  a  temperature  of  38°  C.  (100.4°  F.).  According  to  him, 
the  di astatic  ferment  is  thus  changed  into  glycolytic  ferment.  Lepine 
then  neutralizes  the  solution  with  sodium  bicarbonate,  and  has  the 
patient  drink  the  whole  in  the  course  of  twenty-four  hours.  This 
remedy  is  at  least  harmless.  Lepine  reports  that  he  has  observed 
from  its  use  a  decrease  in  the  glycosuria  and  azoturia,  an  improve- 
ment in  the  general  state,  and  an  increase  in  bodily  weight.  Lepine, 
like  all  reliable  observers,  acknowledges  that  these  results  are 
highly  uncertain. 

Spermin  (Pohl)  is  praised  by  Eulenberg,  Hofmeier,  Hirsch,  and 
others  for  its  beneficial  effects  in  cases  of  neurasthenia.  Its  prop- 
erty of  increasing  the  alkalinity  of  the  blood  f  ought  to  add  to  its 
therapeutic  value  in  severe  cases  of  diabetes,  in  which  something 
besides  possibly  might  be  expected  from  it,  especially  as  regards 
neurasthenic  symptoms.  Spermin — which  is  said  to  exist  to  some 
extent  in  all  organotherapeutic  remedies — has  hitherto,  so  far  as  I 
know,  never  been  used  in  its  pure  form  in  cases  of  diabetes. 


*  Comby  was,  so  far  as  I  know,  the  first  to  employ  this  mode  of  treatment  for 
diabetes. 

f  As  mentioned  by  Senator  and  by  Loewy,  but  considered  by  Strauss  not  10  be  con- 
stant. 


TREATMENT.  289 

Blumenthal  makes  subcutaneous  injections  of  an  extract  of  the 
liver  and  of  the  pancreas,  and  believes  this  to  diminish  the  glyco- 
suria as  much  as  forty  per  cent. 

Gilbert  and  Carnot  administer  an  aqueous  extract  of  the  liver  by 
the  mouth  or  by  the  rectum, — "  opotherapie  hepatigue," — and  believe 
thereby  to  diminish  the  glycosuria. 

Thyroidi7i  is  sometimes  prescribed  in  cases  of  diabetes  by  physi- 
cians of  a  hopeful  and  of  an  experimental  turn  of  mind. 

Mechanotherapy ,  long  neglected,  has  at  last  gained  its  proper 
position  in  many  countries,  and  has  also  been  used  in  the  treatment 
of  diabetes  in  the  forms  of  both  gymnastics  and  massage,  partly  on 
account  of  their  quality  of  diminishing  glycosuria,  partly  on  account 
of  other  effects,  in  my  opinion  more  important.* 

During  the  warm  season  I  have  found  it  most  advantageous  to 
prescribe  gymnastics  (/.  e.,  systematic  exercises)  in  the  form  of 
walks  in  the  open  air.  When  a  diabetic  patient  passes  from  a 
sedentary  life  to  one  of  moderate  exercise,  this,  together  with  the 
usual  effects  on  the  appetite,  circulation,  functions  of  the  bowels, 
and  general  state  of  health,  also  has  some  effect  in  diminishing  the 
glycosuria.  Fatigue  has  a  contrary  effect,  and  must  be  avoided,  and 
the  amount  of  exercise  must  be  regulated  in  proportion  to  the 
patient's  strength,  which  in  advanced  cases  often  is  quite  small.  I 
recommend  two  walks  a  day,  and  think  it  best  for  the  first  to  be 
taken  early  in  the  morning  and  the  last  several  hotirs  before  bed- 
time. A  brisk  walk  just  before  bedtime,  contrary  to  what  is  some- 
times asserted,  has  a  disturbing  influence  on  sleep.     Next  in  value 


*  I  have  set  forth  these  effects  extensively  in  my  "  Handbook  of  Massage,"  to  which 
reference  may  be  made.  I  can  not  enlarge  upon  the  subject  here,  as  this  book  on  dia- 
betes has  already  grown  beyond  its  intended  limits. 

Exercise  was  prescribed  in  cases  of  diabetes  mellitus  in  the"  beginning  of  the  present 
century  by  Marsch,  and  in  more  recent  times  it  has  been  recommended  by  Bouchardat, 
Brouardel,  Zimmer,  Kiilz,  and  others.  I  have  only  recently  had  time  to  investigate  the 
effects  of  general  massage  in  diminishing  glycosuria,  having  used  it  from  time  to  time 
since  Finkler  and  Brockhaus  (1886)  announced  their  results.  While  acknowledging 
the  effect  of  energetic,  prolonged  general  massage  in  causing  diminution  in  the  amount 
of  sugar  in  the  urine,  I  have  not  observed  by  far  so  good  results  as  Finkler  and  Brock- 
haus, and  do  not  consider  a  diminution  from  450  to  120  grams  of  glucose  to  be  possible 
as  a  result  of  mere  massage. 


290  DIABETES    MELLITUS    AND    GLYCOSURIA. 

to  a  moderately  brisk  walk  is  horseback-riding.  The  bicycle,  even 
apart  from  its  liability  to  accidents,  is  less  beneficial. 

In  Scandinavian  countries  Zander's  medicomechanical  institutes 
are  highly  popular  in  the  larger  cities  during  the  winter,  and  they 
have  spread  from  Sweden  to  a  large  part  of  the  civilized  world. 
Their  purpose  is  to  give  gymnastics  and  massage  (especially  the 
different  forms  of  tapotement)  by  machinery.  Here  in  the  North 
we  consider  them  in  many  cases  as  excellent  for  giving  "  mouvement 
cures"  during  our  harsh  winters;  they  are  closed  during  the 
summer.  Most  of  the  patients  suffer  from  weak  heart  or  from  con- 
stipation.* Gymnastics  is  now  taught  in  all  large  communities,  and 
can  easily  be  arranged  in  homes  without  apparatus. 

The  massage  should  be  the  "  general,"  with  effleurage  (stroking) 
frictions,  petrissage  (kneading),  and  tapotement  (striking,  vibrations) 
of  the  greater  part  of  the  body.  The  different  groups  of  muscles 
of  the  limbs  and  of  the  trunk  should  be  subjected  to  this  treatment. 
Frictions  of  the  abdominal  wall  over  the  colon,  with  their  excellent 
influence  on  the  functions  of  the  bowels,  should  be  carefully  prac- 
tised in  the  way  described  by  me  and  now  known  almost  every- 
where. To  exercise  any  influence  at  all  on  the  glycosuria,  and  in 
order  that  its  well-known  beneficial  influence  may  be  exerted  besides 
to  any  great  extent,  general  massage  must  be  practised  for  a  full 
hour  daily,  preferably  in  two  seances.  Under  these  conditions  gen- 
eral massage  requires  but  little  technical  skill,  and  it  may,  after 
some  instruction,  be  performed  by  any  intelligent  and  available 
servant  of  the  same  sex  as  the  patient. 

Hydrotherapy  is  of  considerable  value  in  cases  of  diabetes  for  its 
effect  on  the  nervous  system  and  on  the  skin.  The  diabetic  patients, 
however,  are  always  sensitive  and  must  be  protected  against  exces- 
sive temperatures,  and,  in  general,  the  different  forms  of  baths  to  be 
used  in  these  cases  vary  from  20°  C.  (68.7°  F.)  to  36°  C.  (96.8°  F.). 


*I  shall  entirely  omit  any  description  of  the  details  of  a  "mouvement  cure,"  as 
carried  out  in  Zander's  institutes  or  elsewhere,  but  will  mention  that,  since  I  saw  a 
similar  treatment  recommended  by  some  Italian  physicians  and  by  Charcot,  I  have  some- 
times, in  cases  of  neurasthenic  sleeplessness,  applied  vibration  to  the  head  by  means  of 
Zander's  machines,  and  with  surprisingly  good  results.  The  vibrations  must  be  given 
with  some  force  ;  they  are  contraindicated  by  arteriosclerosis. 


TREATMENT.  29 1 

Different  proceedings,  constituting  a  mild  cold-water- cure,  are  of 
considerable  value. 

A  sheet-batJi  is  sometimes  used  and  generally  given  in  the  morn- 
ing when  the  patient  leaves  his  bed.  A  sheet  wrung  out  of  water 
at  a  temperature  of  about  20°  C.  (68°  F.)  is  for  a  moment  wrapped 
around  the  patient,  who  is  then  energetically  rubbed  with  a  dry 
sheet. 

I  prefer  to  recommend  to  my  diabetic  patients  another  form  of 
bath,  often  and  daily  used  by  healthy  persons  of  the  upper  classes 
in  many  countries  and  by  patients  of  different  kinds.  This  bath  is 
best  taken  in  an  ordinary  sitz-bath,  partly  filled  with  water,  which 
for  sensitive  persons  may  be  kept  at  a  temperature  of  about  20°  C. 
(68°  F.).  The  patient,  on  arising  in  the  morning,  sits  down  in  the 
tub,  squeezes  the  water  out  of  a  large  sponge  three  or  five  times 
upon  his  neck,  and  afterward,  while  drying  the  upper  part  of  his 
body,  stands  in  the  tub.  The  whole  bath  lasts  little  more  than  a 
minute.  At  its  conclusion  the  patient  either  immediately  dresses  for 
a  brisk  walk  or  returns  to  bed  for  a  few  minutes,  until  the  reaction 
following  the  bath  is  fairly  started. 

The  half-bath,  with  gradually  lozvered  temperature,  is  an  excellent 
measure  which  I  often  prescribe  for  diabetic  and  for  neurasthenic 
patients  in  Carlsbad.  The  patient  sits  in  a  large  tub  half  filled 
with  tepid  water  (from  30°  to  35°  C. — from  86°  to  95°  F.)  which, 
for  a  little  while,  is  thrown  upon  his  chest  and  his  back.  Cold 
water  is  then  added,  and  the  patient  for  some  few  minutes  is  sub- 
jected to  energetic  rubbing  of  the  greater  part  of  the  body.  A 
moderately  cold  douche  or  a  dip  in  a  moderately  cold  pond  ends 
the  bath. 

Douches  may  also  be  used  alone.  They  should  be  begun  with 
tepid  water,  the  temperature  being  gradually  lowered  to  as  low  a 
degree  as  the  patient  feels  able  to  endure,  and  the  whole  operation 
lasting  not  longer  than  about  a  minute. 

Sea-bathing  or  lake-bathing  is  to  be  recommended  only  in  mild 
cases  of  diabetes.  It  should  be  indulged  in  only  when  the  temper- 
ature of  both  the  air  and  the  water  is  comparatively  high  and  with 
precautions  against  taking  cold.  Under  these  conditions  sea- 
bathing, in  my  experience,  presents  no  dangers  and  exerts  its  usual 
beneficial  influence. 


292  DIABETES    MELLITUS    AND    GLYCOSURIA. 

The  tepid  bath  at  about  35°  C.  (95°  F.)  can  also  be  used  by- 
diabetics.  It  should  last  about  a  quarter  of  an  hour  and  ought  to 
be  followed  by  a  moderately  cold  douche.  If  taken  in  the  evening 
to  promote  sleep,  the  bath  may  be  given  for  half  an  hour  at  a  tem- 
perature of  36°  or  37°  C.  (96.8°  or  98.6°  F.),  and  it  should  not 
be  followed  by  any  cold-water  application. 

The  electric  bath,  moderately  cold  or  tepid,  and  the  bath  in  car- 
bonated water,  are  both  of  some  value  on  account  of  their  stimulating 
effect. 

The  warm  bath  (at  38°  C. — 100.4°  F. — or  more)  should  be  given 
diabetic  patients  only  in  the  presence  of  incipient  coma,  and  it  ought 
to  last  about  ten  minutes. 

The  addition  of  different  salts,  extracts,  etc.,  to  the  bath  is  often 
pleasant  to  the  patient  and  may  be  of  some  benefit  to  the  skin. 

Electrotherapy  is  employed  in  cases  of  diabetes  in  the  same  way  as 
it  is  in  nervous  diseases.  It  is  generally  the  diabetic  patient's  neuras- 
thenia or  neuritis  that  necessitates  the  application  of  general  or  local 
galvanization  or  faradization.  Like  almost  all  forms  of  treatment, 
this  has  also  been  sometimes  considered  as  diminishing  the  glyco- 
suria ;  D'Arsonval  lately  mentioned  such  a  result  from  the  use  of 
Tesla's  apparatus. 

Many  causes  combine  to  make  the  tissues  of  the  diabetic  patient 
a  poor  soil  for  healing  processes.  The  deleterious  effects  of  hyper- 
glycemia and  blood-toxins,  of  weak  heart,  of  arteriosclerosis,  of  the 
diabetic  endarteritis  in  the  small  vessels,  and  of  defective  nervous  in- 
fluences have  already  been  mentioned.  The  patient's  neurotic  tem- 
perament often  adds  alcoholism  to  his  other  drawbacks.  Suppurat- 
ing and  septic  processes  and  hemorrhages  are  more  common  among 
diabetics  than  among  others.  The  different  physiologic  phases  of 
the  healing  process,  both  in  the  soft  and  in  the  bony  tissues, 
take  place  with  less  energy  than  usual.  The  surgeon,  ready  for  a 
needed  operation,  has  often  replaced  his  knife  on  discovering  sugar 
in  his  patient's  urine,  fearing  to  operate  in  a  case  of  diabetes,  and 
knowing  that  he  would  incur  less  responsibility  by  abstaining  from 
than  by  engaging  in  an  unsuccessful  operation.  Many  a  surgeon 
has  thus  been  saved,  and  many  a  diabetic  patient  who  might  have 


TREATMENT.  293 

been  saved  by  surgery  has  been  sacrificed.  In  the  sixties,  however, 
antisepsis  and  asepsis,  and  the  works  of  Griesinger,  Marchal  de 
Calvi,  and  others  on  the  surgical  comphcations  of  diabetes  began 
to  remove  timidity  of  operating  under  such  conditions.  We  owe 
a  good  deal  to  the  French  in  this  connection,  though  surgical 
nihilism  in  diabetes  has  had  its  advocates  also  in  France  (Landouzy, 
Palle,  and  others).  The  superstition  against  operating  in  cases  of 
diabetes  no  longer  prevails,  and  statistics  prove  that  even  such  deli- 
cate operations  as  those  on  the  eyes  have  almost  as  favorable  an 
outlook  in  the  presence  of  diabetes  as  in  its  absence. 

Operations  on  diabetic  patients  should,  if  the  circumstances 
permit,  be  preceded  by  a  course  of  preparatory  treatment.  In  the 
mild  stage  the  hyperglycemia  should  be  removed  for  a  couple  of 
weeks  previous  to  the  operation,  and  the  carbohydrates  be  w^ith- 
drawn  from  the  food  until  glycosuria  disappears,  if  no  urgent 
reason,  as  set  forth  on  a  preceding  page,  to  the  contrary  exists.  In 
the  severe  stage  the  acidosis  is  to  be  feared  more  than  an  increase  in 
the  constant  and  inevitable  hyperglycemia,  and  consequently  a  fair 
supply  of  carbohydrates  may  be  allowed.  Alcoholic  and  other  bad 
habits  are  to  be  strenuously,  but  wisely,  corrected  during  this  time. 
The  general  state  is  improved  by  all  reconstructive  remedies,  by 
iron  and  arsenic  when  anemia  is  present,  by  nutritious,  easily 
digested  food,  by  general  massage,  etc.,  in  all  cases. 

Asepsis  is  to  be  preferred  to  antisepsis  in  operating  in  cases  of 
diabetes  as  soon  as  the  preparation  of  the  skin  is  ended,  on  account 
of  the  irritating  influence  on  the  diabetic's  sensitive  tissues  by  anti- 
septics and  of  the  patient's  greater  susceptibility  to  the  action  of 
poisons. 

Another  rule  among  surgeons,  in  case  of  diabetes,  is  to  prefer  the 
thermocautery  to  the  knife,  as  soon  as  there  is  a  choice  between  the 
two,  the  better  to  avoid  hemorrhage  (and  infection). 

Diabetic  gangrene,  which  occurs  in  about  ten  per  cent,  of  all  cases 
of  diabetes  (Griesinger),  necessitates  operations  more  often  than 
any  other  complication,  especially  upon  the  lower  limbs.  In  many 
cases  diabetic  and  senile  changes  combine  to  make  the  general  state 
poor.  In  other  cases,  however,  diabetic  gangrene  may  exist 
despite  an  amazingly  good  general  state  of  health.  It  is  often  pos- 
sible to  bring  about  heahng  by  the  usual  local  (and  general)  treat- 


294  DIABETES    MELLITUS    AND    GLYCOSURIA. 

ment  and  to  save  the  limb.*  Surgeons  recommend  djy  bandages 
in  such  cases.  If  operation  becomes  necessary  for  diabetic  gangrene 
in  the  lower  part  of  the  limb,  it  is  usually  performed  above  the  knee. 
Operation  at  the  knee-joint  is  rarely  performed,  surgeons  demand- 
ing a  better  state  of  health  and  better  coverings  than  are  generally 
possessed  by  diabetics.  Godbe  recommends  operation  above  the 
knees  in  all  cases  with  arteriosclerosis. f  In  diabetic  patients  with 
gangrene  in  the  lower  part  of  the  leg  thrombosis  is  quite  common 
at  the  point  of  division  of  the  popliteal  artery,  and  operation  above 
the  knee  is  then  necessary. 


*  Constantin  Panel  has  recently  reported  a  case  of  diabetic  gangrene  in  the  lower 
part  of  the  leg  in  which  a  cure  was  effected  by  means  of  a  permanent  bath  of  oxygen, 
removing  the  india-rubber  apparatus  twice  a  day  in  order  to  wash  the  gangrenous  part 
with  a  warm  solution  of  chloral  (4  :  looo),  by  giving  arsenic  and  lithium  benzoate, 
and  by  enforcing  strict  diet. 

f  As  illustrated  in  one  of  my  cases,  the  operation  below  the  knee  may  sometimes 
yield  good  results  even  in  the  presence  of  distinct  arteriosclerosis. 


ERRATA. 

On  page  56,  seventh  line  from  bottom  of  page,  "other  plausible  explanations"  should 

read  "  other  plausible  explanations  than  the  mere  deficiency  of  oxidation." 
On  page  153,  fourth  line  from  bottom  of  page,  "18  grams  of  nitrogen  "  should  read  "  38 

grams  of  nitrogen." 
On  page  227,  after  the  paragraph  on  acidosis,  the  following  most  important  sentence  has 

been  omitted:  "  The  alkalescency  of  the  blood  may  sink  to  -^^ol  its  normal  value, 

but  is  never  entirely  annihilated." 


TABLE  OF  THE   COMMONEST   KINDS   OF  FOOD, 

SHOWING  CONSTITUENT  PERCENTAGES  OF 

PROTEID,  FAT,  AND  CARBOHYDRATE.^^ 


SIMPLE  ANIMAL  FOODS. 


Meat,  raw  (of  mammals) , 

Meat,  cooked  (roast,  boiled,  etc.), 

Meat,  beef  (smoked), 

Bacon,  raw, 

Lard, 

Meat-powder  (dried), 

Chicken,  raw, 

Pigeon,  raw, 

Duck  (wild),  raw, 

Fish,  fat  (salmon,  eel) ,  raw, 

Fish,  lean  (cod,  pike),  raw, 

Stock  fish,  dried  (cod), 

Oysters, 

Eggs, 

Eggs,  white  of, 

Eggs,  yolks  of,      

Caviar, 

Milk, : 

Milk,  skimmed, 

Cream, 

Whey, 

Butter, 

Cheese,  rich, 

Cheese,      , 

Liver, f 

MIXED  ANIMAL  AND  VEGETABLE_FOODS. 

Omelet  of  eggs,  cream,  and  ham, 

Omelet  of  eggs,  cream,  and  flour  (pancakes),  .    .    . 
Waffles  I  of  cream,  flour,  and  water  (Swedish  style) 

Sausages,  in  general, 

Blood-sausage,       

Liver-sausage, 

Fish-pudding, 


Proteid. 

Fat. 

Carbo- 
hydrate. 

15-22 

1-5-34 



34 

4-5-12 

— 

27 

15-5 

— 

10 

50 

— 

0-3 

99 

— 

75 

— 

— 

20 

4 

— 

22 

I 

— 

22.5 

3 

— 

15-20 

7.5-28 

— 

15-20 

I 

— 

80 

I 

— 

5 

0-3 

2.6 

13 

11 

— 

12 

0-5 

16 

32 

32 

14 

3-5 

3-6 

4.8 

3-5 

0.6 

4.8 

3-5 

20 

3-5 

0.3 

0.2 

5 

0.8 

83 

27 

30 

2-5 

35 

4 

2 

X 

5-30 

~ 

15-5 

19 

I 

12 

10 

25 

10 

12 

25 

17-27 

26-40 

0--5 

12 

"•5 

25 

16 

26.5 

6.; 

10 

12 

II 

*The  figures  are  chiefly  taken  from  Konig's  well-known  work,  in  part  from  the 
publications  of  Munk  and  Ewald,  Jiirgensen,  and  others.  The  table  has  been  prepared 
with  a  view  to  conciseness,  but  it  will  enable,  the  physician  to  form  an  idea  as  to  the 
caloric  value  of  almost  any  kind  of  food. 

■f  Liver,  as  prepared  for  the  table,  contains  only  a  small  percentage  of  glycogen. 

J  Waffles,  Swedish  style,  when  made  exclusively  of  cream,  flour,  and  water,  usually 
contain  about  twenty-five  per  cent,  of  carbohydrate  ;  but  they  are  extremely  voluminous 
and  light  and  form  a  good  substratum  for  butter  with  a  comparatively  very  small  supply 
of  carbohydrate.  Except  when  a  rigid  diet  is  to  be  observed,  they  can  sometimes  be  used 
by  diabetics  instead  of  bread. 

295 


296 


DIABETES    MELLITUS    AND    GLYCOSURIA. 


SIMPLE  VEGETABLES  AND  FRUITS  (Uncooked). 


Jerusalem  artichokes  (topinambour) , 

Lettuce, 

Cucumbers, 

Asparagus, 

Spinach,f 

Radishes, 

Celery  (leaves), 

Onions,      

Mushrooms  (agaricus), 

Cabbage  (white), 

Cauliflower, 

Cabbage  (green), 

Cabbage  (Brussels  sprouts),    .    .    . 

Cabbage   (red), 

Parsley,       

Tomatoes, 

String-beans, J 

Peanuts  (Arachis  hypogsea),    .    .    . 

Almonds, 

Walnuts,    . 

Hazelnuts, 

Cranberries, 

Raspberries, ,    .    . 

Currants  (red  and  white),    .... 

Blueberries, 

Strawberries, 

Gooseberries, 

Plums, 

Cherries, 

Apples, 

Pears, 

Oranges  (juice), 

Peaches,     

Bananas, 

Grapes, 

Carrots,  

Turnips, 

Potatoes, .    . 

Sweet  potatoes, 

Beans  (seeds,  dried), 

Peas    (seeds,  dried), 

Apples,  dried, 

Pears,  dried, 

Prunes, 

Raisins, 

Figs, 


Proteid. 


2 

1-4 

I 

1.8 

3 

1.2 

4.6 

2.7 

3-6 

1-9 

2-5 

4 

4.8 

1.8 

3-7 

1.2 

2.7 

28.2 

24.2 

16.4 

15-6 

0.1 

0.4 

0.5 
0.8 
0.9 

o-S 
0.4 
0.7 
0.4 
0.4 
0.4 
0.65 

1-9 
0.6 
I 

2.1 

1.8 

1-3 

24-3 

22.8 

1-3 

2 

2.2 

2.4 

5 


Fat. 


O.I 

0-3 

O.I 

0.2 
0.5 

O.I 

0.8 
0.3 
0.3 

0.2 

03 
0.9 

0-5 
0.2 
0.7 

0-3 

0.1 

46.4 

53-7 
69.2 
66.5 


Carbo- 
hydrate. 


0.6 

0.2 
O.I 

0.2 

0-3 
1.6 
1.8 
0.8 
0-3 
0.5 
0.6 


15-2* 

2.2 

2-3 
2.6 

3-5 
3-8 
10 

6.5 
6.8 
4.9 

4-5 

11. 6 
6.2 
5-9 
7.4 
4-1 
6.6 
8 

7.2 
7-9 
9 

1-5 
5-3 
6.3 
5-9 
3-4-4 
8.4 
8.2 

12 
12 
II. 8 

5-54 
"•5 
23 
16.3 

9.4 

11. 7 
20.6 
23 
49 
52.4 
59-8 
58.8 
62.3 
62 
45-3 


*The  carbohydrate  in  the  Jerusalem  artichokes  consists  of  inulin,  levulose,  and  gum. 
They  are  thus  especially  suitable  for  the  diabetic's  table.  Tn  many  fruits  the  carbo- 
hydrate consists  partly  of  levulose  in  addition  to  starch  and  glucose. 

t  The  figures  refer  to  the  green  leaves  of  Spinacia  oleracea — not  to  spinach  prepared 
with  flour. 

J  The  figures  refer  to  string-beans  with  full-grown  seeds.  Before  the  seeds  are  developed 
string-beans  contain  much  inosite,  but  only  an  insignificant  amount  of  true  carbohydrate, 
and  they  are  an  important  item  in  the  diabetic's  bill  of  fare. 


PROTEID,    FAT,    AND    CARBOHYDRATE    IN    FOOD. 


297 


SIMPLE  VEGETABLES  AND  FRUITS  (Uncooked). 
(Continued.) 


Chestnuts, 

Coffee  (burnt), 

Tea  (dried  leaves), 

Chocolate,  unsweetened, 

Chocolate,  sweet,      

CEREALS.PREADS,  ETC. 

Rice,  dried, 

Sago,  dried, 

Indian  corn  (maize), 

Macaroni,  dried, 

Flour  of  the  Soya-bean, 

Rye-flour, 

Wheat-flour,      

Oatmeal,  dry  (coarse), 

Rye-bread, 

Wheat-bread, 

Graham  bread, 

English  biscuits, 


Proteid. 


5-5 
12.2 
21 

5 
12.3 


9 

0.8 
11.67 

9 

3-4 
12.8 
10.5 

IS 

6.1 
6.1 
6 
7.2 


Fat. 


1.4 
12 

3-6 

IS-2 

52.3 


0.8 

5-5 

0.3 

16.4 

2.3 

1-3 

6 

0.4 

0.4 

0.3 

9-3 


Carbo- 
hydrate. 


38.3 
13-4 
17.6 
74.8 
28.3 


77.8 
76.7 
29.6 

81.3 
87.1 

64-73 
49.2 

51 

39-41 
75-1 


LIQUORS. 


Percentage. 


Vol. 


Weight. 


Sugar 

AND 

Extract. 


Cognac,   French  brandy, 
Whisky,  American,  .    .    . 

"        Scotch,   .    .    .    . 

"        Irish, 

Cider, 

Beers  and  ales,     .    .    .    . 

Porters,      

Rhine  wines,  white,  .  . 
Rhine -wines,  red,  .  .  . 
Beaune  (Burgundy),  . 
St.  Emilion  (Bordeaux), 
Swiss  wine,  white,  .  .  . 
Swiss  wine,  red,  .  .  .  . 
Austrian  wine,  red,  .    .    . 

Sherry, 

Madeira,    ....... 

Marsala, 

Port  wine, 

Malaga,      

Champagne,      

Curacao, 

Arrac-punch  (Swedish),  . 


55 
60 

50-3 
49.9 


9 

8.7 

9.6 

9-4 
9-5 


55 
26.3 


47-3 
52.2 
42.8 

42.3 

4.2 

2.5-4.9 

5-3 
II. 4 
10 


17 
15-6 
16.4 
16.4 
"•5 
9 


0.6 


4-7.2 
8.9 
2.6 

3-4 

2.7 

3 

1-9 
1.6 
2.7 

5 

8.6 
8 
10.2 

30- 3 

24.8 

57 
69.8 


19 


PERSONAL  REGISTER. 


Abeles,  26,  38,  65,  177,  178,  i^ 

Abelmann,  105,  167 

Achard,  60,  243 

V.  Ackeren,  129,  135,  209 

Acri,  117 

Aladoff,  34 

Albertoni,  116,  117,133,  223 

Albic,  220 

Aldehoff,  165,  279 

Althaus,  90,  94 

Amann,  219 

Ambrosiani,  10 

Andral,  49,  55,  159 

Anger,  98 

Anselme,  138 

Anstoots,  63 

Araki,  13,  51,  56,  57,  58,  68 

Argutinsky,  186 

Armanni,  no,  113,  116 

Arnschink,  171 

Arthaud,  33,  48,  49 

Arthur,  49 

Arthus,  180 

Asher,  32 

Auche,  94,  97 

Auerbach,  94 

Ausset  de  Cerenville,  288 


Baisch,  26 

Barlow,  36,  62 

Barral,  181,  188,  191,  192,  284 

Basham,  286 

Battistini,  288 

Baum,  37 

Baumann,  217 

Beale,  63 

Becker  (O.),  119,  120 

Begbie,  41 

Bence  Jones,  11,  13,  26,  159 

Benda,  no 

Benzi,  286 

Bequerel,  35,  36 

Beranger-Ferand,  15 


252 


Berger,  119 

Bernard,  Claude,  11,  13,  24,  29,  31,  33, 

49.  54.  57,  66,  67,  105,  169,  173,  176, 

183,  191,  203,  216,  229 
Bernstein,  279 
Berthier,  87 
Bettman,  36,  102 
Bial,  170,  180,  182 
Bidder,  11 
Biedl,  243 
Biefel,  56 
Bischoff,  II,  171 
Bischofswerder,  216 
Blair,  18 
Blake,  54 
Blau,  82 
Bleibtreu,  235 
Bleile,  170,  181 
Blocq,  36 
Blot,  65 

Blumenthal,  289 

Boccardi,  97,  108,  113,  116,  117,  177 
Bock,  53,  58,  181,  187 
Boecker,  229 
Boedeker,  217 
Bohm,  34,  38,  68,  176,  181 
Bollinger,  50 
Bond,  35 
Bonome,  113 
Borchert,  229,  232 
Bordier,  62,  63 
Bose,  17 
Bouchard,   12,  14,  53,  55,  74,  76,  91, 

119,  120,  135,  228,  284 
Bouchardat,  12,  13,203,  216,  267,  281, 

286 
Bouchut,  62 
Bouveret,  121 
Brault,  137,  177 
Bremer,  loi,  244 
Breul,  26 
Brieger,  133 
Brietzke,  186 
Bright,  105 
Brockhaus,  203,  289 
Brogniart,  216 


299 


300 


PERSONAL    REGISTER. 


Brouardel,  37,  193,  289 

Brown-Sequard,  191 

Briicke,  11,  26 

Brunelle,  53,  54 

Brunner,  135 

Buchheim,  171 

Budde,  115,  216 

Budge,  34,  200 

Bull,  William  T.,  105,  135 

Bunge,  170,  185,  217 

Burdel,  64 

Burger,  231 

Burghardt,  68 

Burns,  94 

Bury,  90,  94 

Bussenius,  203 

Butte,  33,  34,  48,  49.  ^82,  183,  192 

Buzzard,  90,  94 


Calmette,  18,  64 
Camplin,  274 
Cantani,  12,  14,  41,  T] ,  267 
Cantlie,  18 
Caparelli,  165 
Carnot,  289 
Caroe,  16 
Carrion,  138 
Cartier,  53,  54 
Casal,  57 
de  Cassaet,  286 
Cavazzani,  A.,  35,  183 
Cavazzani,  E.,  35,  183 
Celsus,  10 

Charcot,  24,  63,  90,  94,  97,  216,  257 
Charrin,  129 
Chauffard,  137 

Chauveau,  12,  32,    33,   49,    165,   166, 
181,  185,  186,  189,  194-198.  229 

Chittenden,  54,  182 

Chvostek,  36 

Coignard,  52,  216 

Colasanti,  218 

Colenbrander,  192 

Colrat,  49 

Comby,  288 

Coolen,  60,  61 

Coranda,  133 

Cornevin,  62 

Couturier,  49 

Cowley,  135 

Cramer,  66 

Cremer,  60,  174,  175.  185 

Crichton-Browne,  87 

Cruikshank,  10 

Cunningham,  36 

Curee,  54 


Cyon,  34 
Czapek, 208 


D. 


Dalton,  180 
D'Arsonval,  292 
Dastre,  49,  56,  179,  192 
Davis,  N.  S.,  81 
Davy,  loi 
Decker,  63 
De  Dominicis,  165 
Deichmiiller,  133 
De  Jong,  35,  200 
Delamare,  60 
Demant,  57,  176 
Demme,  35 
Derignac,  219 
Deutschmann,  119,  120 
Devie,  113,  219 
Dickinson,  96 
Dieulafoy,  128 
Dittrich,  108 
Dobson,  10,  77,  284 
Doch,  57,  174 
Donkin,  277 
Dreyfus-Brisac,  286 
Dufour,  183 
Dufresne,  58 
Dujardin-Beaumetz,  127 
Dumontpellier,  36 
Duponc,  34 
Duponchet,E64 
V.  Dusch,  id,  131 

E. 

Ebstein,  12,  14,  37,  86,  116,   117,  175. 

216 
Eckhard,  32,  33,  55,  57,  58 
Edel,  187 

Edwards,  Mile.  Blaine,  35 
Ehrlich,  117,  I77,  178 
Eichhorst,  63,  66,  94,  97.  98 
Ehotson,  105 
V.  Engel,  215 
Engelmann,  231 
Erlenmeyer,  91 
Ernst,  115 

Eulenburg,  35,  55.  288 
Ewald,  51,  58,  178,  181,  187,295 
Exner,  49 


Fahlberg,  279 
Falkenberg,  38 
Feilchenfeld,  54 


PERSONAL    REGISTER. 


301 


Fere,  36,  133 

Ferraro,  97,  100,  108,  113,  116 

Fichtner,  116 

Fick,  186 

Finkelstein,  229,  232 

Finkler,  37,  135,  203,  289 

Finlayson,  86 

Finn,  174 

Fischer,  37,  62 

Fitz,  no 

Fleiner,  134 

Fleischer,  57 

Fles,  105 

Fleury,  98 

Flint,  186 

Fodor,  129 

Foerster,  119 

Forsell,  268 

Foster,  203 

Fraentzel,  175 

Frank,  Peter,  64,  78 

Franque,  158 

Frazer,  34 

Frerichs,  11,  12,  34,  35,  36,  52,  54,  55, 
56,  62,  63,  69,  93,  96,  98,  105,  108, 
117,  131,  132,  172,  176,  177,  188 

Freund,  58,  190 

Fiirbringer,  77,  103,  218,  229 

Futterer,  96 


Gabritschewski,  178 

Gaglio,  57,  165 

Gallard,  137 

Gans,  37,  104,  180 

Gara,  63 

Garofalo,  57 

Garrod,  76 

Gascuel,  83 

Gathgens,  229,  231 

Gaudard,  118 

Gelmo,  62 

Geppert,  52 

Gerhardt,  11,  133 

Gerhardt,  D.,  102,  212,  227 

Geyer,  237 

Gianturco,  113 

Gib,  Paul,  37 

V.  Gieson,  117 

Gilbert,  289 

Gilles  de  la  Tourette,  257 

Girard,  182 

Giron,  81 

Glenard,  in 

Gley,  60,  62,  165,  229,  288 

Gmelin,  10,  54 

Godlee,  294 


Goerlitz,  120 

Golowin,  49 

Golz,  52 

Goodhart,  96 

Goolden,  36,  63,  158 

Gorup-Besanez,  208 

Graefe,  119 

Graf,  54 

Graham,  17,  61 

Graser,  62 

Griesinger,  12,  25,  36,  102,  293 

Grohe,  178 

Grube,  19,  ^6,  114,  282 

Gruber,  207 

Gubler,  63 

Guckelberg,  215,  230 

Gueneau,  63 

Gueudeville,  10 

Guiard,  115 

Guignard,  129 

Guinon,  93,  94 

Gull,  107 

Gumpertz,  88 

Giirtler,  57 


H. 

Habershon,  69 

Hale  White,  207 

Haller,  135 

Hallervorden,  133 

Hammarsten,  170,  215 

Hammerschlag,  loi 

Hanot,  113,  137,  138 

Hansemann,  no 

Harden,  127 

Harley,  49,  55 

Hartge,  116 

Hartsen,  105,  106 

Hartz,  216 

Hasse,  56 

Haughton,  229 

Hay  craft,  207 

Hedon,  32,  120,  165,  166,  193 

Heidenhain,  81 

Heine,  159 

Heinemann,  109 

Heintz,  63 

Heller,  170 

Henrat,  98 

Henriot,  235 

Hensay,  97 

Hensen,  181 

Hergenhahn,  49,  173,  174,  176 

Hernandez,  Gonsalez,  137 

Heyneman,  Newton,  185 


302 


PERSONAL    REGISTER. 


Heyse,  207 

Higgins,  32,  74 

Hirsch,  288 

Hirschberg,  119,  122,226 

Hirschfeld,  105,  170,  213 

Hodgkin,  81 

Hoesslin,  14 

V.  Hoesslin,  94 

Hoffmann,  55,  220,  252 

Hoffmann,  G.  A.,  12,  34,  38,  53,  58, 

176,  181,  187,  214 
Hofmeier,  288 
Hofmeister,  24,  30,  65,  67,   171,   200, 

203 
Holmgren  (E.)  219,  237 
Holsti,  65 
Honigmann,  104 
Hoppe,  173 

Hoppe-Seyler,  52,  177,  igo 
Horner,  121 
Huber,  50 
Hubner,  180 
Hiibner,  15 
Huchard,  35 
Hugonenq,  52,  219 
Hundhausen,  275 
Hunt,  W.,  81 
Huppert,  14,  63,  177 
Husband,  29,  66 


Ingerslev,  159 
Irisawa,  56 
Isenflamm,   159 
Israel,  100 


Jaccoud, 14 

Jacobson,  119 

Jacobson,  Otto,  64 

Jacoby  (New  York),  86 

Jacoby  (Strassburg),  58,  69 

V.  Jaksch,  53,  57,   loi,   133,  215,   217, 

226 
James,  A.,  loi,  131 
Jasper,  285 
Joffroy,  97 
Johannowski,  65 
Johnson  (St.),  217 


K. 


Kahler,  30,  31,  35,  56 
Kaiser,  210 
Kalm,  219 


Kalmus,  97 

Kaltenbach,  65 

Kaposi,  81,  127 

Kassel,  215 

Kassowitz,  129 

Kaufmann,  12,  32,  33,  49,  165,  166, 
167,  181,  185,  189,  194-198,  229 

Kausch,  69,  165,  174,  175,  179 

Kemmerich,  214 

Kessler,  53 

Kinnicutt,  158 

Kirchner,  124 

Kirmisson,  83 

Kirsten,  65 

Kisch,  66 

Klebs,  34 

Klemperer,  58,  60,  67,  69,  115,  207 

Knies,  119,   120 

Kbbner,  170 

Konig,  121,  295 

Koninck,  59 

Kbrner,  124 

Kossel,  279 

Kowalewski,  54 

Kratschmer,  24,  177,  229 

Kraus,  36,  192,  243 

Kraus,  I.,  79 

Kravkow,  215 

Kuhn,  124 

Kiihne,  26,  31,  177 

Kiilz,  E.,  17,  30,  33,  34,  38,  52,  53, 
132,  133, 157,  159,  170,  175, 176, 181 
203,  205-209,  213,  224,  229,  230 

Kumagawa,  185 

Kunkler,  36 

Kuntzel,  53 

Kupper,  172 

Kussmaul,  54,  131,  133 


Laache,  36 
Laborde,  158 
Lallier,  35,  36 
Lamanski,  34 
Lambert,  54,  182 
Lancereaux,  36,  108,  135,  2i 
Landouzy,  293 
Landwehr,  219 
Lang,  66,  179 
Langendorff,  57, '165 
Lapique,  138 
Laseque,  107 
Laub,  53 
Laulanie,  235 
Laves,  176,  235 
Lavoisier,  11 


PERSONAL    REGISTER, 


303 


Leber,  119,  122,  123 

Leblanc,  15 

Lecanu,  102,  212 

Leconte,  54 

Lecorche,  14,  94,  98,  100,  286 

Le  Goff,  287 

Legroux,  39 

Lehmann,  11,  6^] ,  181,  214,  217 

Leichtentritt,  97 

Lemaire,  65,  219 

Le  Nobel,  105,  134,  135,  209 

Leo,  209,  220,  235 

Lepine,  12,  33,  58,  69,  95,    165,   181, 

190,  191,  193,  220,  284,  288 
Leroux,  157,  159 
Letulle,  137,  203 
Leube,  178,  219,  229 
Leudet,  35 
Leval-Piquechef,  94 
Levene,  61 
Lewaschew,  284 
Lewin,  54 
Levin,  171 
Ley  den,  90,  94,  97 
Lichtheim,  134,  221 
Liebig,  11,  174 
Lindemann,  175 
Lionville,  57 
Livierato,  232 
Loewy,  245,  288 
Lohnstein,  247 
Loye,  192 
Lubinoff,  98 

Luchsinger,  58,  172,  174 
Ludwig,  36,  187 
Liihdorf,  275 

Lusk,  60,  61,  170,  171,  181,  224 
Lussanna,  182 
Lustig,  34 


M. 

McDonnel,  38,  173,  182 

McGregor,  10 

Magendie,  1 1 

Magnus-Levy,  51,  115,235 

Maitland,  10 

Manchot,  51 

Mannkopf,  35,  d'j 

Maquenne,  207 

Marcet,  14 

Marcus,  66 

Marcuse,  165 

Marechal  de  Calvi,  81,  293 

Marie,  94 

Marinesco,  36 

Marinian,  91 


Marklen,  103 

Marsh,  289 

Marthen,  116 

Martin-Damourette,  52 

Martineau,  282 

Masoin,  53 

Matrai,  190 

Mauthner,  122,  209 

May.  175 

Mayer,  52 

Meissner,  182 

V.  Mering,   12,  51,   52,   53,  55,  59,  60, 

61,  105,  135,  136.  164,  170,  174,  177, 

181,  185,  187,  188,  203,  229 
Mermod,  14 
Metroz,  192 

Meyer,  Jacques,  35,  36,  100 
Mialhe,  281 
Michael,  35,  96 
Minkowski,    12,  38,   52,  105,  106,   133, 

135,    136,    164-168,    177,    193,    202, 

207,  223,  229 
Minnich,  134 
Minor,  97 

Miura,  185,  199,  200,  213,  224 
Montuori,  182 
Morat,  33,  34,  183 
Moriggia,  66 

Moritz,  26,  59,  60,  185,  200 
Morrison,  69 
Moscatelli,  217 
Mosler,  229 
Mosse,  182 
Mosso,  U.,  14 
Miiller,  Fr.,  106,  115,  171 
Munck,  34 
Munk,  171,  184,  295 
Miinzer,  50,  53,  132,  133,  229 
Musculus,  170 


N. 


Nasse,  loi,  210,  231 

Naunyn,  14,  29,  32,  35,  36,  37,  38,  50, 
52,  66,  69,  71,  94,  102,  103,  107,  III, 
115,  116,  118,  134,  174,  203,  216, 
268 

Nebelthau,  174,  175,  176 

Neisser,  177 

V.  Nencki,  13,  174,  234 

Nesbi,  116 

Nettelbladt,  158 

Neubauer,  220 

Neumann,  28,  58,  98 

Neumeister,  182 

Neusser,  49,  102 


304 


PERSONAL    REGISTER. 


Key,  65 

Nicolas,  10 

Niedergesass,  157 

Niedieck,  33 

Nommes,  191 

Nonne,  91 

V.  Noorden,  12,  58,  185,  224 

Nordenson,  121,  123,  149,  162 

Nylander,  26 


O. 

Obici,  116 

Ogden,  32,  74 

Ollivier,  35,  56 

van  Oordt,  35 

Oppenheim,  35,  93,  186 

Oppler,  247 

Orth,  135 

Otto,  171,  172,  181,  187,  188 


Palle,  293 
Palm  a,  207 
Panas,  36 
Panel,  294 
Papanikolau,  119 
Paracelsus,  10 
Parkes,  186 
Parmentier,  138 
Parrot,  158 
Paschutin,  177 
Paton,  Noel,  182 
Pautz,  170,  232 

Pavy,  12,  13,  19,  20,  32,  34,  36,  38,  52, 
61,  69,  159,  174,  178-183,  186,  190, 
215,275 

Peiper,  34 
Penzoldt,  57 

Percy,  98 

Pettenkofer,  11,  214,  229,  232 

Petters,  133 

Peyrot,  81 

Pfliiger,  174,  186 

Philipeaux,  63 

Pichon,  58 

Pick,  77 

Pickhardt,  187 

Pierre-Marie,  36,  137,  287 

Pincus,  34 

Pisenti,  116,  117 

Pitres,  82 

Poll,  62,  63 

PoUak,  56.  66 

PoUatschek,  52 


Popper,  13 

Praussnitz,  59,  60,  171,  177,  185 

Prevost,  63 

Price,  94,  97 

Prout,  63,  75,  218,  267,  274 

Purdy,  17,  19,  20 


Ouinquaud,  53,  189 


Rabuteau,  54 

Range,  64 

Raynor,  87 

Reale,  38 

Rebitzer,  68 

V.  Rechenberg,    232 

V.  Recklingshausen,  35 

Redard,  63 

Redon,  62,  157,  160 

Reich,  229 

Reichhardt,  219 

Reignault,  11,  186,  234 

Reiset,  11,  186,  234 

Reynoso,  28,  53,  63 

Richardiere,  35,  37,  281 

Richardson,  35,  56,  120 

Riegel,  107,  108 

Rienzi,  38 

Riess,  216 

Ringer,  36 

Ritter,  55,  60,  182,  185 

Roberts,  159,  247 

Robin,  282,  286 

Roger,  59,  62 

Rohmann,  170,  208 

Rolf,  52 

Rollo,  10,  264 

Roos,  26 

Roque,  113,  219 

Rosenbach,  53 

Rosenbaum,  176 

Rosenblath,  82,  loi 

Rosenfeld,  61,  226 

Rosenheim,  171 

Rosenstein,  57,-91,  94.  io4.  io8,  229 

Ross,  26,  90,  94 

Rossa,  66 

Rovere,  84 

Rubner,  11,  171,  172,  200,  232 

Rumpf,  133,  218,  227 

Rupstein,  230 

Ryndsjun,  34 


PERSONAL    REGISTER. 


305 


Saikowski,  53,  57 

Salkowski,  175,  214 

Salomon,  172 

Samoje,  63 

Sampacchia,  113 

Sandmeyer,  97,  105,  165,  174,  177 

Sauer,  56,  57 

Saundby,  17,  96,  no,  113 

Savage,  87 

Scharlau,  36 

Schenk,  186,  188 

Schermetjewski,  13 

Schierbeck,  14 

Schiff,  13,  31.  32,  33,  36,  38,  56,  57,  182 

Schilder,  26 

Schindelka,  15 

Schindler,  ']'] 

Schirmer,  119 

Schmidt-Rimpler,  119,  122 

Schmidt,  G.,  11,  181 

Schmitz,  20,  25,  49,  76,  115,  284 

Schultze,  14 

Schultzen,  13 

Schiitz,  35 

Schwarz,  168 

Schwiening,  180 

Scolozoboff,  54 

See,  Germain,  60 

Seegen,  11,  12,  29,  35,38,  58,  71,  118, 

171-178,  183,  186,  187,188,  194,200, 

208,  275 
Segalas,  10 
Seitz,  105,  no 
Semmola,  63 
Senator,  39,  55,  67,  84,  115,   159,  217, 

288 
SenfF,  56,  57 
Senn,  N.,  105,  135 
Settenbom,  82 
Seyfert,  62 
Sieber,  13,  234 
Siebert,  36 
Siebold,  55 
Silver,  105 
Simons,  10 
Sinety,  65 
Smith,  35,  93 
Sobeiran,  10 
Socin,  174,  175 
Soldani,  35 
Sotniskewski,  177 
Souques,  93 
Spiegelberg,  65 
Spitzer,  192 
Spitzka,  35 

Stadelmann,  52,  no,  133,  220,  227 
Startz,  216 


I  Steinhaus,  n3 
Stern,  63,  157 
Stokvis,  173 
Strasser,   132,  133,  229 
Strassmann,  213 
Straub,  Walther,  57 
Straus,  35,  37,  53,  58,  n6,  234 
Stray  nowski,  118 
V.  Striimpell,  37,  90 
Subbotin,  214 
Susruta,  10,  127 
Sydenham,  64 


T. 

Tangl,  49 

Taylor,  96 

Tcherinoff,  173,  174 

Tebb,  170 

Telz,  55 

Tenbaum,  231 

V.  Terray,  63 

Teschemacher,  58 

Tessier,  25 

Thiel,  60 

Thierfelder,  229,  237 

Thiermesse,  15 

Thiroloix,  165,  166,  229,  il 

Tholozan,  18 

Thomas,  90 

Thompson,  11 

Tiedeman,  10 

Tiegl,  180 

Toepfer,  58,  140 

Toll,  148 

Tollens,  133 

Topinard,  35 

Toralbi,  88,  202 

Trambusti,  116 

Traube,  n,  220 

Triboulet,  138 

Troye,  221,  228 

True,  120 

Tscherinow,  49,  173 


U. 


Uhle,  229 
Ulrich,  219 


Vahl,  207 
Vamossy,  57 
Vas,  63 
Vauquelin,  10 


3o6 


PERSONAL    REGISTER. 


Velisch,  38,  165 

Vergely,  94 

Verron,  95 

Vespa,  1"] 

Vetlesen,  240 

Viaud-Grand-Marais,  282 

Vogel,  219,  220 

Vogler,  36 

Voisin,  57 

Voit,  12,  170,  174,  210,  i\\,  229,  232 

Voit,  E.,  214 

Voit,  Fr.,  171,  174,  206,  207,  232,  243 

Voit,  Hans,  34 

Vulpian,  63 


W. 

Wagner,  63 

Walkow,  217 

Walter,  52,  133 

Watson,  159 

Wedenski,  26,  209,  219 

Weichselbaum,  35 

Weil,  243 

Weintraud,  12,  104,  165,  179,211,221, 

234 
Weir-Mitchell,  84,  119 
Weiss,  174,  185 
Werther,  177 
West,  159 


Whitehouse,  54 

Wickham-Legg,  177 

Wiersma,  177 

Wiesinger,  119 

V.  Wildt,  124 

Williams,  66 

Williamson,  97,  loi,  245 

Willis,  10,  281 

Winogradoff,  57,  217 

Wislicenus,  186 

V.  Wittisch,  49 

Wolf,  208 

Wolf  berg,  174 

WoUaston,  10 

Wood,  Horatio,  91,  127 

Worm-Miiller,  26,  30,  46,  199,  200,  204 

Worms,  14,  284 

Woroschiloff,  173 

Woroschilski,  54 


Z. 

Zander,  257,  290 

Zenker,  103 

Ziemssen,  90,  94 

Zillesen,  56 

Zimmer,  13,  54,  68,  69,  191,  203,  208 

Zinn,  62 

Zuntz,  57,  62,  184,  186 


INDEX 


Acetone,  6i, 

221 


[,   133,    168,  214,   215, 


Acetonuria,  168,  169 
Achroodextrin,  170 
Acid,  acetic,  217 
butyric,  217 
carbonic,  56,  234 
dextronic,  52 
diacetic,  52,  53,  61,  133,  168,  214, 

221,  228 
formic,  215 
glycosuric,  217 

glycuronic,  51,  52,  179,  218,  239 
hippuric,  217 
homogentisinic,  217 
hydrochloric,  52 
lactic,  51,  52,  55,  57,    168,  179, 

218 
levuUnic,  215 
mucous,  52 
orthro-n  i  t  r  o-phenyl-propionic, 

52 
oxahc,  52,  218 
/?-oxybutyric,    52,    61,   133,   168, 

214,  221 
phloretic,  59 
propionic,  217 
prussic,  52 
salicylic,  52 
sugar,  52 
sulphuric,  52 

coupled        (etherous, 
aromatic),     53,    59, 
172,  219 
in  sulphates,  53,  172, 
219 
Acidity  of  gastric  juice,  104,  108 

of  urine,  219,  227 
Acidosis,  72,  168,  227,  263 
Acids,  fatty,  52,  217 
Aciduria,  227 
Acne,  127 

Addison's  disease,  68 
Adiposity,  140 
Age,  19,  158 
Akromegaly,  36 


Albuminuria,  51,  52,  59,  76,  114,  228, 

248 
Alcohol,  54,  203,  212,  232 
Alcoholism,  137 
Alkalies,  51-53,  259,  281 
Alkapton,  217,  239 
Altitude,  20 
Amaurosis,  123 
Amblyopia,  95,  123 
Ammonia,  55,  61,  224,  227 
Amyl  nitrite,  51,  55 
Analgesia,  91 
Anatomy  of  blood,  loi 

of  brain,  95,  96 

of  gastro-intestinal     tube, 
108 

of  heart,  100 

of  kidneys,  116 

of  liver,  no 

of  lungs,  103 

of  muscles,  128 

of  nerves,  97,  98 

of  ovaries,  118 

of  pancreas,  108 

of  skin,  126 

of  spinal  marrow,  96,  97 

of  spleen,  113 

of  testicles,  118 

of  uterus,  118 

of  vessels,  loi 
Anesthesia,  91 
Aneurysms,  35 
Angina  pectoris,  99 
Anhidrosis,  79,  91,  126 
Annulus  Vieusseni,  34 
Anorexia,  80,  107 
Anthrax,  63 

Aromatic  substances,  172 
Arsenic,  53,  203,  280 
Arterial  blood,  sugar  of,  182,  188 
Arteriosclerosis,  99 
Artery,  ligation  of  femoral,  38 

of  gastroepiploic,  49 
of  splenic,  49 
Asphyxia,  38,  55,  158 
Assimilation,  200,  203,  241 
Asteatosis,  79,  126 


307 


3o8 


INDEX. 


Asthenopia,  124 

Atrophy,  acute  yellow,  of  the  liver,  49 

Autophagia,  81,  168 

Azoturia,  228 


Balanitis,  118 

Balanoposthitis,  118,  160 

Basophilia,  perinuclear,  102 

Bile,  49 

Blood,  acids  in,  133,  224 
corpuscles,  loi 
glycogen  in,  177 
hemoglobin  of,  138 
specific  gravity  of,  loi 
sugar  of,  187 
tests  of,  244 

Bones,  128 

Brain,  32,  35,  36,  86,  95 

Bread, 274 

Breath,  84 

Bulimia,  79 

Butter,  271 

Butyric  acid.     See  Acid,  Butyric. 


Cachexia,  68 

Calculi  in  gall-ducts,  37,  49,  79 

in  kidneys  and  urinary  ducts, 

in  pancreas,  109 

Calories,  232 

Cane-sugar.     See  Saccharose. 

Carbohydrate,  24,   57,    105,  170,  184, 
232 

Carbon  dioxid.     See  Acid,  Carbonic. 
monoxid,  56 

Carbuncle,  83 

Casts,  renal,  248 

Cataract,  119-121,  160 

Chalazion,  124 

Chloral,  51,  55 

Chloralamid,  51,  55 

Chloroform,  55 

Cholera,  63,  64 

Chorea,  35 

Circulation,  98 

Cirrhosis  of  kidneys,  115 
of  liver,  50,  137 
of  pancreas,  109,  137 

Classes,  social,  22 

Climate,  20 

Cold,  20,  68 

Coma,  85,  131-133,  161,  258 

Constipation,  106,  258 

Cramp,  89 

Crises  gastriques,  106 

Croup,  63,  158 


Crura  cerebelli,  31,  32 

cerebri,  32 
Crystallose,  279 
Curare,  57 

Cysticercus  racemosus,  35 
Cystitis,  115 

D. 

Decubitus,  83 

Deiter's  nucleus,  31 

Delphinin  (=methyl  delphinin),  57 

Dextrin,  170,  219 

Diabetes  alternans,  44,  216 

bronze-colored,  137,  138 

constitutional,  136 

decipiens,  78 

fat,  136 

gastro-intestinal,  137 

gouty,  136 

hepatogenic,  137 

herpetic,  136 

in  animals,  15 

infantilis,  157-164 

insipidus,  28,  39,  67 

mild,  10,  129,  202,  220 

muscular,  137 

neurogenic,!  134 

pancreatic,   134,  164-169 

periodic,  44 

renal,  137 

severe,  10,  130,  202,  220 
Diacetic  acid.     See  Acid,  Diacetic. 
Diamins,  220 
Diet,  203,  227,  261 
Digestion,  104,  170 
Digestive  organs,  104-114 
Dilatation  of  stomach,  104 
Diphtheria,  62,  158 
Diplopia,  95 
Disaccharids,  170 
Distribution  of  diabetes,  16-18 
Diuretin,  58 
Dysentery,  62 

E. 
Ears,  124 

Eczema,  41,  91,  124,  127 
Electrotherapy,  292 
Emotions,  22,  37,  38,  159,  203 
Encephalomalacia,  36 
Endarteritis,  97,  loi,  138 
Energy.     See  Vital  Force. 
Enuresis,  158 
Epilepsy,  36,  86 
Episcleritis,  124 
Erysipelas,  63,  84 
Erythema,  127 

nodosum,  63 


INDEX. 


309 


Ether,  55 

Etiology  of  diabetes  mellitus,  16-25. 
(Race — mode  of  life — sex — age — 
climate — heredity — profession  — ex- 
cesses— emotions — sedentary  life — 
diet — exposure — trauma — sunstroke 
— adiposity — gout.) 

Excesses,  22,  23,  203 

Exophthalmic  goiter,  36,  86 

Exposure,  24 

Exudates,  203 

Eyes,  1 18-124 

F. 

Fat,  60,  105,  170,   171,   184,  209,  212, 

232 
Fatigue,  68,  203 
Feces,  58,  105,  135 
Fermentation,  000 
Ferments  in  blood,  180,  191 

in  liver,  179 

in  urine,  220 
Fesselungsglycosurie,  38 
Fever,  166,  203 
Fibrin,  57 
Food,  170,  189 

Frequency  of  diabetes  mellitus,  15-18 
Furunculosis,  41,  83 

G. 

Galactose,  207,  240 
Gall-stones,  37,  49,  79,  112 
Ganglion,  celiac,  34,  35 

inferior  cervical,  34 
superior  cervical,  34 
thoracic,  34 
Gangrene,  81,  91,  103,  293 
Gastric  juice,  108 
Gingivitis,  85 
Glands,  gastric,  108 
peptic,  108 
salivary,  38 
thyroid,  38 
Glucose,  167,  170,  184,  206,  232,  239 
Glycemia,  29,  188 
Glycogen,   52,  97,1168,  170,  172,  173- 

180 
Glycolysin,  191 
Glycolysis,  191-193 
Glycosuria,  alimentary,    29,   48,    173, 
199 
cachectic,  68 
cardiac,  28,  58 
concomitant,  28 
experimental,  31 
fatigue,  68 
fetal,  66 
from  cold,  68 


Glycosuria,  gouty,  67 

hepatogenous,  48 
in  animals,  37 
marasmic,  68 
nervous,  functional,    37- 
48 
organic,  30-37 
pancreatic,  165,  166 
puerperal,  65 
renal,  69 
senile,  68 

simple,  9,  42-48,  242 
starvation,  67 
toxic,  50-62.    (From  acids 
— metals   and   salts   of 
alkalies,      phosphorus, 
arsenic,  mercury,  lead, 
uranium  —  alcohol, 
ether,      chloroform, 
chloral,      chloralamid, 
amyl  nitrite,  ammonia 
— carbonic    acid,    car- 
bon monoxid — curare, 
strychnin,      delphinin, 
morphin,   veratrin,    er- 
gotin,  caffein — diuretics 
thyroidin,      tuberculin, 
pancreatin,    fecal     ex- 
tract— phloridzin     and 
phloretin.) 
Glycosurias,  26,  204 
Glycosuric  acid.  See  Acid,  Glycosuric. 
Glycuronic   acid.      See  Acid,  Glycu- 

ronic. 
Gout,  25,  39,  67 
Graves'  disease.     See  Exophthalmic 

Goiter. 
Gum,  animal,  219,  240 
Gummata,  63 
Gums,  85 

H. 

Hair,  127 

Heart,  98,  100 

Hemianopsia,  95 

Hemoglobin,  138 

Hemorrhage,  94,  100,  124 

Hemosiderosis,  loi,  138 

Heredity,  21,  159 

Herpes,  91,  124,  127 

History,  10-15 

Homogentisinic  acid.     See  Acid,  Ho- 

mogentisiftic. 
Hordeolum,  124 
Hunger,  79 
Hydrotherapy,  290 
Hygiene,  255 
Hyperesthesia,  90,  124,  125 


3IO 


INDEX. 


Hyperglycemia,  29,  48,  49,  56,  57,  71, 

165,  190 
Hyperidrosis,  91 
Hypermetropia,  121 
Hypochondriasis,  87 
Hypoglycemia,  29,  33,  49,  56,  61 
Hysteria,  88 


Ichthyosis,  127 

Icterus,  53 

Impetigo,  127 

Impotence,  117 

Incontinence.     See  Emiresis. 

Infection,  25 

Infectious  diseases,  62,  159 

Influenza,  62,  64 

Inosit,  207 

Insomnia,  41,  256 

Inulin,  207 

Invertin,  170 

Iridocyclitis,  123 

Iritis,  123 

Irritability,  41 

Isomaltose,  219 

K. 

Keratitis,  123 
Kidneys,  69,  114-117 
Knee-jerk.     See  Reflexes. 
Kreatin,  217 
Kreatinin,  217,  239 


Lactaciduria,  53,  57 

Lactose,  62,   66,  167,    171,   206,   208, 

232,  239 
Lactosuria,  65,  199 
Laios,  208 
Lassitude,  128 
Lead,  53 
Leucin,  219 
Leukemia,  68 
Leukocytes,  177,  178 
Leukocytosis,  loi 

Levulose,   167,  171,  206,  208,  239,  279 
Levulosuria,  167,  199 
Lichen,  127 
Life-insurance,  243 
Lipaciduria,  218 
Lipemia,  102,  212 
Lipuria,  212,  218 
Liver,  48,   50,  57,  59,   no,  137,    173, 

214 
Lobus  diabeticus,  31,  32 

hydruricus,  31,  32 

opticus,  32 
Lungs,   103 


Luxuries,  23 
Lymphangitis,  84 
Lyssa,  63 

M. 

Malaria,  62,  64,  137 

Mai  perforant,  83,  91 

Maltose,  167,  170,  209,  219,  239 

Maltosuria,  135,  199,  209 

Mannite,  207 

Marasmus,  68,  102,   161,   204 

Marriage,  254 

Massage,  203,  290 

Mastication,  104 

Masturbation,  158 

Measles,  62 

Mechanotherapy,  289 

Melancholia,  87 

Meningitis,  35 

Meningomyelitis,  36 

Mental  treatment,  255 

Mercury,  53 

Metabolism,  168 

Metallic  salts,  53 

Migraine,  89 

Milk,  276 

Milk-sugar.     See  Lactose. 

Monosaccharids,  170 

Morbus  gravesi.      See  Exophthalmic 

Goiter. 
Morphin,  57,  61 
Mouth,  79.  84 
Mucin,  214,  215 
Muscles,  128,  203 
Mydriasis,  121 
Myelitis,  36 
Myocardium,  99 
Myopia,  121 

N. 
Nails,  91,  128 
Nephritis,  60 
Nephrolithiasis,  115 
Nerve,   abducent,  95 

crural,  91 

depressor  of  the  pneumogas- 
tric,  33 

dorsal,  34 

facial,  95 

oculomotor,  95 

optic,  122 

pneumogastric,  31,  33 

sciatic,  33 

splanchnic,  34 

supraorbital,  89 

sympathetic,  34,98,  183 

tibial,  97 
Nervous  symptoms,  86-95 
Neuralgia,  37,  88,  158 


INDEX. 


311 


Neurasthenia,  39,  70,  88,  106 
Neuritis,  go,  97,  102 
Neuroses,  36,  37,  87,  106 
Neurotabes,  94 
Nitrobenzol,  51 
Nitrogen,  166,  170,  233 
Nitrotoluol,  51 
Nuclein,  214,  215 
Nutritive  needs,  168,  232,  260 


O. 

Obesity,  25,  39,  66 

Oidium  albicans,  160 

Operations,  292 

Ophthalmic  goiter,  86 

Opium,  203,  280 

Orchitis,  118 

Organotherapy,  288 

Osteomalacia,  231 

Osteoporosis,  85,  129 

Otalgia,  125 

Otitis,  124,  125 

Ovaries,  118 

Oxalic  acid.     See  Acid,  Oxalic. 

Oxaluria,  41,  45,  218 

/3-Oxybutyric  acid.     See  Acid,  ^-oxy- 

butyric. 
Oxygen,  234 

P. 

Pancreas,  108,  164-169 
Pancreatic  juice,  105,  168 
Pancreatin,  58 
Paralysis,  91 

agitans,  35 

general,  progressive,  35 
Paraplasma,  57,  172 
Paraplegia,  91 
Paresthesia,  88 
Paronychia,  128 
Pedunculi  cerebelli,  32 

cerebri,  32 
Pemphigus,  127 
Pentoses,  175,  215,  219,  240 
Peptonuria,  53 
Pericementitis,  85 
Periostitis,  85 
Perspiration,  231 
Pertussis,  63,  158 
Petechiae,  127 
Phenacetin,  203 
Phimosis,  118,  160 
Phlegmon,  84 
Phloretin,  59 
Phloridzin,  59,  166 
Phloroglucin,  59 


Phlorose,  59 

Phosphaturia,  230 

Phosphorus,  49 

Phthisis  (pulmonary  tuberculosis),  102 

Pigment,  138 

Piqure,  Bernard's,  31 

Pityriasis,  127 

Pneumaturia,  115 

Pneumonia,  63,  103,  161 

Pollakiuria,  41,  78 

Polydipsia,  76 

Polyneuritis,  90 

Polyuria,  31,  58,  76,  207 

Potatoes,  276 

Potency,  sexual,  89 

Pregnancy,  66,  118,  254 

Presbyopia,  121 

Professions,  21 

Prognosis,  63,  138-141,  160 

Prophylaxis,  253 

Propionic  acid.     See  Acid,  Propionic. 

Proteids,  57,  105,  170,  171,  184,  201, 

212,  232 
Pruritus,  126 

Pseudo  angina  pectoris,  99 
Pseudotabes,  93 
Psoriasis,  127 
Psychoneuroses,  21,  87 
Ptomains,  220 
Ptosis,  95 
Pulse,  'JT ,  98,  131 
Pupil,  Argyll  Robertson,  92 
Purpura,  127 
Pylethrombosis,  49 
Pyorrhea,  alveolar,  85 
Pyrocatechin,  5,  217 


Quotient  of  respiration,  185,  235 


R. 

Race,  17 

Raynaud's  disease,  83,  91 
Recovery,  65,  160 
Reflexes,  92 
Remedies,  280 
Respiration,  131,  234 
Respiratory  organs,  102 
Retinitis,  122 
Rupia,  127 

S. 

Saccharids,  170,  174 
Saccharin,  279 
Saccharomyces  apiculatus,  239 


312 


INDEX. 


Saccharose,  167,  170,  206,  232 

Saccharosuria,  46,  47,  199,  201 

Salicylic  acid.     See  Acid,  Salicylic. 

Saliva,  104,  202 

Sanatoriums,  256 

Scai-let  fever,  62,  158 

Sciatica,  36,  88 

Scleritis,  124 

Sclerosis,  multiple,  35 

Secretions,  79,  104 

Sedentariness,  23 

Senility,  68 

Sensibility,  91 

Sex,  19,  159 

Simulation,  252 

Sleep,  32,  256 

Spinal  cord,  32,  36,  57,  91,  96,  97 

Spleen,  113 

Spondylitis,  37 

Sputa,  203 

Stages  of  diabetic  dystrophy,  9,   10, 

42-47,  129 
Starch,  52,  170,  206,  232 
Starvation,  24,  67,  159,  167,  183,  203 
Sterility,  118 
Stools,  105,  134 

Strains,  emotional  and  intellectual,  22 
Strychnin,  51,  57 
Sugar  in  blood,  10,  187 
in  liver,  11,  180 
in  urine,  9,  11,  73.     See  Galac- 
tose, Glucose,  Lactose,  Levu- 
lose.  Maltose,  Saccharose. 
Sulphates,  172 
Sulphonal,  56 

Sulphuric  acid.    See  Acid,  Sulphuric. 
Sunstroke,  25 
Sweat,  202 
Sweets,  24,  158 

Symptoms  of  diabetes,  70-138 
Syphilis,  35,  63,  287 
Syzygium  jambulanum,  62,  168,  284 


T. 

Tabes  dorsalis,  35 

Tears,  202 

Teeth,  42,  85 

Temperature,  85,  160 

Test,  Barfoed's  (glucose),  239 

Bernard-Seegen's  (glucose),  238 
Biebrich's  (blood,  color),  245 
Bremer's  (blood,  color),  244 
Ehrlich-Biondi's  (blood,  color), 

245 
Esbach's  (albumin),  248 
Fischer's  (glucose),  237 


Test,  Gerhardt's(diacetic  acid),  11,71, 
240,  247 
Heller's  (albumin),  248 
Kjeldahl's  (nitrogen),  248 
Nylander's  (glucose),  237,  239 
Robert's  (glucose),  247 
Troemmer's  (glucose),  237 
Williamson's  (blood,  color),  245 
Worm-Miiller's  (glucose),  237 

Testicles,  118 

Theories,  12-14,  I79.  194-198 

Thirst,  42,  76 

Thyroidin,  58 

Tongue,  84 

Toxins,  71,  220,  221 

Transmutation,  86 

Trauma,  32,  140,  159 

Tuberculin,  58 

Tuberculosis,  68,  102,  137,  161 

Tumors  (new  growths),  35 

Typhoid,  62,  64 

Tyrosin,  219 


U. 

Urea,  216 

Uric  acid,  216,  239 

Urinary  organs.  114-117 

Urine,  73-76,  160 
color,  75 
density,  75 
quantity,  ']'] ,  246 
specific  gravity,  75,  246 
substances  in.     See  under  the 
different  headings :   Acetone, 
Albumin,  Alkapton,  Ammo- 
nia,   Butyric    Acid,     Casts 
{renal').    Dextrin,    Diacetic 
Acid,      Diamins,       Fatty 
Acids,   Ferment,     Glycogen, 
Glucose,     Glycosuric    Acid, 
Glycuronic  Acid,  Gtim,  Hip- 
puric  Acid,  Homogentisinic 
Acid,  Indoxyl,    Inosite,  Iso- 
maltose.  Lactic  Acid,  Lactose, 
Laios,      Levulose,      Leucin, 
Maltose,  Oxalic  Acid,  ft-  Oxy- 
butyric  Acid,  Pentoses,  Pto- 
mains  Pyrocatechin,  Reduc- 
ing Substances,   Saccharose, 
Skaioxyl,  Sulphuric  Acid  {in 
sulphates  and  coupled).  Tox- 
ins,  Urea,    Uric  Acid,    Uro- 
bilin, Urochloralic  Acid,  Uro- 
leucin. 
toxicity,  220 

Urobilin,  219 

Urochloralic  acid,  239 


INDEX. 


313, 


Uroleucin,  219 
Urticaria,  91 
Uterus,  118 


Vaccinia,  63 

Variola,  63 

Vein,  portal,  181,  189 

Veins,  hepatic,  181,  182,  188 

in  general,  181,  188 
Ventricle,  fourth,  of  the  brain,  31,  95 

(stomach),  104 
Veratrin,  51,  58 
Vermis,  32 
Vessels,  arterial,  181,  188 


Virility,  41 
Vital  force,  184-187 
Vulnerability,  81 
Vulvitis,  118,  160 


W. 

Water,  231,  278 
Weighing,  249 
Weight  of  body,  80 


Xanthoma  tuberosum  diabeticum,  127 


CATALOGUE 
No.  1. 


READ  "SPECIAL  NOTE"  BELOW. 

NOVEMBER,  1899. 


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additions  by  the  author,  and  revisions  and  additions  by  Dr.  Henry  Leff- 
mann,  Professor  of  Chemistry  and  Metallurgy  in  the  Pennsylvania  College 
of  Dental  Surgery,  and  in  the  Wagner  Free  Institute  of  Science,  Philadel- 
phia, etc.,  with  many  useful  tables.     8vo.     1898.  Cloth,  $4.50 
Vol.  II — Part  I,     Fixed   Oils,   Fats,  Waxes,  Glycerol,  Soaps,  Nitroglycerin, 
Dynamites  and  Smokeless  Powders,  Wool-Fats,  Degras,  etc.     Third  Edi- 
tion, with  many  useful  tables.     Revised  by  Dr.  Henry  Leffmann,  with 
numerous  additions  by  the  author.     8vo.     1899.                              Cloth,  $3.50 
Vol.  II — Part  II.     Hydrocarbons,  including  Terpenes,  Resins  and  Camphors, 
Benzene  Derivatives,  Phenols,  etc.     Third  Edition,  Revised  by  Dr.  Henry 
Leffmann,  with  additions  by  the  author.                                      Nearly  Ready. 
Vol.  Ill — Part  I.     Acid  Derivatives  of  Phenols,  Aromatic  Acids,   Dyes  and 
Coloring  Matters.     Third  Edition,  Revised  by  I.  Merritt  Mathews,  Pro- 
fessor of  Chemistry  and  Dyeing  at  the  Philadelphia  Textile  School,  with 
many  additions  by  the  author.                                                          hi  Prepa?-aiion . 
Vol.  Ill — Part   II.      The   Amines    and   Ammonium    Bases,  Hydrazines    and 
Derivatives.    Bases  from  Tar.    The  Antipyretics,  etc.    Vegetable  Alkaloids, 
Tea,   Coffee,  Cocoa,   Kola,  Cocaine,   Opium,  etc.      Second  Edition.     8vo. 
1892.                                                                                                          Cloth,  $4.50 
Vol.  Ill — Part  III.      Vegetable   Alkaloids   concluded,    Non-Basic  Vegetable 
Bitter  Principles.     Animal  Bases,  Animal  Acids,  Cyanogen  and  its  Deriva- 
tives, etc.     Second  Edition.     8vo.     1896.                                          Cloth,  $4.50 
Vol.   IV.      The   Proteids   and   Albuminous   Principles.      Proteoids   or   Albu- 
minoids.    Second  Edition,  with  elaborate  appendices  and  a  large  number 
of  useful  tables.     8vo.     1898.                                                               Cloth,  ^4.50 

SPECIAL   NOTICE-     These  editions  of  Allen  are  issued  by  us  in  connection  with  him  and  his 

London    Publishers  ;   they  include  much    new  material   and   copyright 

matter,  and  are  the  only  authorized  and  up-to-date  editions.     Circular  upon  application. 


p.  BLAKISTON'S  SON  &-  CO:S 


ARLT.  Clinical  Studies  on  Diseases  of  the  Eye.  By  Dr.  Ferd.  Ritter  von 
Arlt,  Authorized  Translation  by  Lyman  Ware,  m.d.,  Surgeon  to  the  lUinois 
Charitable  Eye  and  Ear  Infirmary,  Chicago.     Illustrated.     8vo.  Cloth,  $1.25 

ARMATAGE.  The  Veterinarian's  Pocket  Remembrancer.  By  George  Arma- 
TAGE,  M.R.c.v.s.     Second  Edition,     32mo.  Boards,  $1.00 

BALLOU.  Veterinary  Anatomy  and  Physiology.  By  Wm.  R.  Ballou,  m.d.. 
Late  Prof,  of  Equine  Anatomy,  New  York  Coll.  of  Veterinary  Surgeons,  Physician 
to  Bellevue  Dispensary,  and  Lecturer  on  Genito-Urinary  Surgery,  New  York 
Polyclinic,  etc.  With  29  Graphic  Illustrations.  i2mo.  A'0. 12  f  Quiz-Compend? 
Series.  Cloth,  .80.     Interleaved,  for  the  addition  of  Notes,  $1.25 

BAR.  Antiseptic  Midwifery.  The  Principles  of  Antiseptic  Methods  Applied  to 
Obstetric  Practice.  By  Dr.  Paul  Bar,  Paris.  Authorized  Translation  by  Henry 
D.  Fry,  m.d.,  with  an  Appendix  by  the  author.     Octavo.  Cloth,  $1.00 

BARRETT.  Dental  Surgery  for  General  Practitioners  and  Students  of  Medicine 
and  Dentistry.  Extraction  of  Teeth,  etc.  By  A.  W.  Barrett,  m.d.  Third 
Edition.     86  Illustrations.     i2mo.  Cloth,  $1.00 

BARTLEY.  Medical  and  Pharmaceutical  Chemistry.  Fifth  Edition.  A  Text- 
book for  Medical  and  Pharmaceutical  Students.  By  E.  H.  Bartley,  m.d.,  Pro- 
fessor of  Chemistry  and  Toxicology  at  the  Long  Island  College  Hospital ;  Dean 
and  Professor  of  Chemistry,  Brooklyn  College  of  Pharmacy ;  President  of  the 
American  Society  of  Public  Analysts;  Chief  Chemist,  Board  of  Health,  of 
Brooklyn,  N.  Y.  Revised  and  Improved.  With  Illustrations.  Glossary'-  and 
Complete  Index.     i2mo.  Cloth,  $3.00  ;  Leather,  $3.50 

Clinical  Chemistry.  The  Chemical  Examination  of  the  Saliva,  Gastric  Juice, 
Feces,  Milk,  Urine,  etc.,  with  notes  on  Urinary  Diagnosis,  Volumetric 
Analysis  and  Weights  and  Measures.     Illustrated.     i2mo.  Cloth,  gi.oo 

BEALE.     On  Slight  Ailments ;  their  Nature  and  Treatment.     By  Lionel  S.  Beale, 

m.d.,  F.R.S.,  Professor  of  Practice,  King's   Medical   College,  London.     Second 

Edition.     Enlarged  and  Illustrated.     Svo.  Cloth,  $1.25 

One  Hundred  Urinary  Deposits,  on  eight  sheets,  for  the  Hospital,  Labora- 

tor}',  or  Surgery.     New  Edition.     4to.  Paper,  $2.00 

BEASLEY'S  Book  of  Prescriptions.  Containing  over  3100  Prescriptions,  collected 
from  the  Practice  of  the  most  Eminent  Physicians  and  Surgeons — English, 
French,  and  American  ;  a  Compendious  History  of  the  Materia  Medica,  Lists  of 
the  Doses  of  all  Officinal  and  Established  Preparations,  and  an  Index  of  Diseases 
and  their  Remedies.     By  Henry  Beasley.     Seventh  Edition.  Cloth,  $2.00 

Druggists'  General  Receipt  Book.  Comprising  a  copious  Veterinary  Formu- 
lary ;  Recipes  in  Patent  and  Proprietary  Medicines,  Druggists'  Nostrums, 
etc.;  Perfumery  and  Cosmeticb  ;  Beverages,  Dietetic  Articles  and  Condi- 
ments ;  Trade  Chemicals,  Scientific  Processes,  and  an  Appendix  of  Useful 
Tables.     Tenth  Edition.     Revised.  Clpth,  %i.oo 

Pharmaceutical  Formulary  and  Synopsis  of  the  British,  French,  German, 
and  United  States  Pharmacopoeias.  Comprising  Standard  and  Approved 
Formulae  for  the  Preparations  and  Compounds  Employed  in  Medical  Prac- 
tice.    Twelfth  Edition.  Cloth,  S2.00 

BEEVOR.  Diseases  of  the  Nervous  System  and  Their  Treatment.  By  Chas. 
Edward  Beevor,  m.d.,  f.r.c.p..  Physician  to  the  National  Hospital  for  Para- 
lyzed and  Epileptic;  Formerly  Assistant  Physician  University  College  Hospital, 
London.     Illustrated.     i2mo.  Cloth,  $2.50 

BIDDLE'S  Materia  Medica  and  Therapeutics.  Including  Dose  List,  Dietary  for 
the  Sick,  Table  of  Parasites,  and  Memoranda  of  New  Remedies.  By  Prof. 
John  B.  Biddle,  m.d..  Late  Prof,  of  Materia  Medica  in  Jefferson  Medical  College, 
Philadelphia.  Thirteenth  Edition,  thoroughly  revised  in  accordance  with  new 
U.  S.  P.,  by  Clement  Biddle,  m.d..  Assistant  Surgeon,  U.  S.  Navy.  With  64 
Illustrations  and  a  Clinical  Index.    Octavo.  Cloth,  $4.00;  Sheep,  $5.00 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  7 

BIGELOW.  Plain  Talks  on  Medical  Electricity  and  Batteries,  whh  a  Thera- 
peutic Index  and  a  Glossary.  By  Horatio  R.  Bigelow,  m.d.,  Fellow  of  the 
British  Gynaecological  Society,  etc.   43  Illus.,  and  a  Glossary.    2d  Ed.    Cloth,  $i.oo 

BIRCH.  Practical  Physiology.  An  Elementary  Class  Book.  Including  Histol- 
ogy, Chemical  and  Experimental  Physiology.  By  De  Burgh  Birch,  m.d.,  cm., 
F.R  S.E.,  Professor  of  Physiology  in  the  Yorkshire  College  of  the  Victoria  Uni- 
versity ;  Examiner  in  Victoria  University  ;  additional  Examiner  in  Edinburgh 
University,  etc.     With  62  Illustrations.     i2mo.  Cloth,  $1.75 

BLACK.  Micro-Organisms.  The  Formation  of  Poisons.  A  Biological  study  of 
the  Germ  Theory  of  Disease.     By  G.  V.  Black,  m.d.,  d.d.s.  Cloth,  .75 

BLACKBURN.  Autopsies.  A  Manual  of  Autopsies,  Designed  for  the  use  of  Hos- 
pitals for  the  Insane  and  other  Public  Institutions.  By  I.  W.  Blackburn,  m.d., 
Pathologist  to  the  Government  Hospital  for  the  Insane.    Illustrated.    Cloth,  $1.25 

BLODGETT'S  Dental  Pathology.  By  Albert  N.  Blodgett,  m.d..  Late  Prof,  of 
Pathology  and  Therapeutics,  Boston  Dental  Coll.    33  Illus.    i2mo.    Cloth,  $i.2C) 

BLOXAM.  Chemistry,  Inorganic  and  Organic.  With  Experiments.  By 
Charles  L.  Bloxam.  Edited  by  J.  M.  Thompson,  Professor  of  Chemistry  in 
King's  College,  London,  and  A.  G.  Bloxam,  Head  of  the  Chemistry  Depart- 
ment, Goldsmiths'  Institute,  London.  Eighth  Edition.  Revised  and  Enlarged. 
281  Engravings,  20  of  which  are  new.     8vo.  Cloth,  $4.25  ;  Leather,  $5.25 

BRACKEN.     Outlines  of  Materia  Medica  and  Pharmacology.     By  H.  M. 

Bracken,  Professor  of  Materia  Medica  and  Therapeutics  and  of  CHnical 
Medicine,  University  of  Minnesota.     Svo.  Cloth,  I2.75 

BRAMWELL.  Anaemia  and  Some  of  the  Diseases  of  the  Blood-forming 
Organs  and  Ductless  Glands.  By  Byrom  Bramwell,  m.d.,  f.r.c.p.  (Ed.), 
F.R.S.  (Ed.),  Physician  to  the  Royal  Infirmary,  Edinburgh  ;  Lecturer  on  the 
Principles  and  Practice  of  Medicine  and  on  CUnical  Medicine  in  the  School  of 
the  Royal  Colleges,  Edinburgh,  etc.,  etc.     Octavo.     450  pages.  Cloth,  $2.50 

BROOMELL.    Anatomy  and  Histology  of  the  Human  Mouth  and  Teeth.    By 

Dr.  I.  N.  Broomell,  Professor  of  Dental  Anatomy,  Dental  Histology,  and 
Prosthetic  Technics  in  the  Pennsylvania  College  of  Dental  Surgery.  With  284 
Handsome  Illustrations,  the  majority  of  which  are  original.     Large  Octavo. 

Cloth,  I4.50 

BROWN.     Medical  Diagnosis.     A  Manual  of  Clinical  Methods.     By  J.  J.  Graham 

Brown,  m.d.,  f.r.c.p.,  Asst.  Physician  Royal  Infirmary;  Lecturer  on  Principles 

and   Practice  of  Medicine  in  the  School  of  Medicine  of  the  Royal  Colleges, 

Edinburgh,  etc.     Fourth  Edition.    112  Illustrations.     i2mo.  Cloth,  $2.25 

BROWN.  Elemehtary  Physiology  for  Nurses.  By  Miss  Florence  Haig  Brown, 
Late  in  Charge  Nurse  Department,  St.  Thomas'  Hospital,  London.  With  many 
Illustrations.  Cloth,  .75 

BRTJBAKER.  Physiology.  A  Compend  of  Physiology,  specially  adapted  for  the 
use  of  Students  and  Physicians.  By  A.  P.  Brubaker,  m.d.,  Adjunct  Professor 
of  Physiology  at  Jefferson  Medical  College,  Prof,  of  Physiology,  Penn'a  College 
of  Dental  Surgery,  Philadelphia.  Ninth  Edition.  Revised,  Enlarged,  and  Illus- 
trated.    No.  4,  f  Quiz- Compend?  Series.    i2mo.      Cloth,  .80;  Interleaved,  $1.25 

BTJLKLEY.  The  Skin  in  Health  and  Disease.  By  L.  Duncan  Bulkley,  m.d., 
Attending  Physician  at  the  New  York  Hospital.     Illustrated.  Cloth,  .40 

BURNET.  Foods  and  Dietaries.  A  Manual  of  Clinical  Dietetics.  By  R.  W. 
Burnet,  m.d.,  m.r.c.p.,  Physician  to  the  Great  Northern  Central  Hospital. 
With  Appendix  on  Predigested  Foods  and  Invalid  Cookery.  Full  directions  as 
to  hours  of  taking  nourishment,  quantity,  etc.     Second  Edition.  Cloth,  $1.50 

BURNETT.  Hearing,  and  How  to  Keep  It.  By  Chas.  H.  Burnett,  m.d..  Prof, 
of  Diseases  of  the  Ear  at  the  Philadelphia  Polyclinic.     Illustrated.         Cloth,  .40 

BUXTON.  On  Anesthetics.  A  Manual.  By  Dudley  Wilmot  Buxton,  m.r.c.s., 
m.r.c.p.,  Ass't  to  Prof,  of  Med.,  and  Administrator  of  Anesthetics,  University 
College  Hospital,  London.     Third  Edition,  Illustrated.     i2mo.  In  Press. 


p.  BLAKISTON'S  SON  6-  CO:S 


BUTLIN.  The  Operative  Surgery  of  Malignant  Disease.  By  Henry  T. 
BUTLIN,  F.R.C  S.,  Ass't  Surgeon  to,  and  Demonstrator  of  Surgery  at,  St.  Bartholo- 
mew's Hospital,  London,  etc.,  assisted  by  James  Berry,  f.r.c.s.,  Wm.  Bruce- 
Clarke,  M.B  ,  F.R.C.S.,   A.  H.  G.  DORAN,   F.R.C.S.,    PERCY   FURNIVALL,   F.R.C.S., 

W.  H.  H.  Jessop,  M.B.,  F.R.C.S.,  and  H.  J.  Waring,  b.Sc,  f.r.c.s.  Second 
Edition,  Revised  and  Rewritten.     Illustrated.  Nearly  Ready. 

BYFORD.  Manual  of  Gynecology.  A  Practical  Student's  Book.  By  Henry  T. 
Byford,  M.D.,  Professor  of  Gynecology  and  Clinical  Gynecology  in  the  College 
of  Physicians  and  Surgeons  of  Chicago ;  Professor  of  Clinical  Gynecology, 
Women's  Medical  School  of  Northwestern  University,  and  in  Post-Graduate 
Medical  School  of  Chicago,  etc.  Second  Edition,  Enlarged.  With  341  Illustra- 
tions, many  of  which  are  from  original  drawings  and  several  of  which  are  col- 
ored.    i2mo.     596  pages.  Cloth,  $3.00 

BYFORD.  Diseases  of  Women.  By  the  late  W.  H.  Byford,  a.m.,  m.d.  Fourth 
Edition.     306  Illustrations.     Octavo.  Cloth,  $2.00 

CALDWELL.  Chemical  Analysis.  Elements  of  Qualitative  and  Quantitative 
Chemical  Analysis.  By  G.  C.  Caldwell,  b.s.,  Ph.D.,  Professor  of  Agricultural 
and  Analytical  Chemistry  in  Cornell  University,  Ithaca,  New  York,  etc.  Third 
Edition.     Revised  and  Enlarged.     Octavo.  Cloth,  $1.50 

CAMERON.  Oils  and  Varnishes.  A  Practical  Handbook,  by  James  Cameron, 
f.i.c.     With  Illustrations,  Formulas,  Tables,  etc.     i2mo.  Cloth,  $2.25 

Soap  and  Candles.     A  New  Handbook    for  Manufacturers,  Chemists,  Ana- 
lysts, etc.     54  Illustrations.     i2mo.  Cloth,  $2.00 

CANFIELD.  Hygiene  of  the  Sick-Room.  A  book  for  Nurses  and  others.  Being 
a  Brief  Consideration  of  Asepsis,  Antisepsis,  Disinfection,  Bacteriology,  Immu- 
nity, Heating  and  Ventilation,  and  kindred  subjects,  for  the  use  of  Nurses  and 
other  Intelligent  Women.  By  William  Buckingham  Canfield,  a.m.,  m.d., 
Lecturer  on  Clinical  Medicine  and  Chief  of  Chest  Clinic,  University  of  Mary- 
land, Physician  to  Bay  View  Hospital  and  Union  Protestant  Infirmary,  Balti- 
more.    i2mo.  Cloth,  $1.25 

CARPENTER.  The  Microscope  and  Its  Revelations.  By  W.  B.  Carpenter, 
m.d.,  f.r.s.  Eighth  Edition.  By  Rev.  Dr.  Dallinger,  f.  r.  s.  Revised  and 
Enlarged,  with  800  Illustrations  and  many  Lithographs.     Octavo.        Preparing. 

CATJTLEY.  Feeding  of  Infants  and  Young  Children  by  Natural  and  Arti- 
ficial Methods.  By  Edmund  Cautley,  m.d..  Physician  to  the  Belgrave  Hospital 
for  Children,  London.     i2mo.  Cloth,  $2.00 

CAZEATJX  and  TARNIER'S  Midwifery.    With  Appendix,  by  Munde.    The 

Theory  and  Practice  of  Obstetrics,  including  the  Diseases  of  Pregnancy  and 
Parturition,  Obstetrical  Operations,  etc.  By  P.  Cazeaux.  Remodeled  and  re- 
arranged, with  revisions  and  additions,  by  S.  Tarnier,m.d.  Eighth  American, 
from  the  Eighth  French  and  First  Italian  Edition.  Edited  by  Robert  J.  Hess, 
m.d..  Physician  to  the  Northern  Dispensary,  Phila.,  etc.,  with  an  Appendix  by 
Paul  F.  Munde,  m.d..  Professor  of  Gynecology  at  the  New  York  Polyclinic. 
Illustrated  by  Chromo-Lithographs,  Lithographs,  and  other  Full-page  Plates 
and  numerous  Wood  Engravings.     8vo.  Cloth,  $4.50;  Full  Leather,  $5.50 

COBLENTZ.  Manual  of  Pharmacy.  A  Text-Book  for  Students.  By  Virgil 
CoBLENTZ,  A.M.,  PH.D.,  F.C.S.,  Professor  of  Chemistry  and  Physics;  Director  of 
Pharmaceutical  Laboratory,  College  of  Pharmacy  of  the  City  of  New  York. 
Second  Edition,  Revised  and  Enlarged.    437  Illustrations.    Octavo.     572  pages. 

Cloth,  $3.50;  Sheep,  $4.50;  Half  Russia,  $5.50 

The   Newer   Remedies.     Including  their   Synonyms,  Sources,   Methods  of 

Preparation,  Tests,  Solubilities,  and  Doses  as  far  as  known.     Together  with 

Sections  on  Organo-Therapeutic  Agents  and  Indifferent  Compounds  of  Iron. 

Third  Edition,  very  much  enlarged.     Octavo.    Just  Ready.         Cloth,  $1.00 

COHEN.  The  Throat  and  Voice.   By  J.  Solis-Cohen,  m.d.  IUus.   i2mo.   Cloth,  .40 

COLLIE,  On  Fevers.  A  Practical  Treatise  on  Fevers,  Their  History,  Etiology, 
Diagnosis,  Prognosis,  and  Treatment.  By  Alexander  Collie,  m.d.,  m.r.c.p., 
Lond.,  Medical  Officer  of  the  Homerton  and  of  the  London  Fever  Hospitals. 
With  Colored  Plates.     i2mo.  Cloth,  J2.00 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  9 

COOPER.  Syphilis.  By  Alfred  Cooper,  f.r.c.s.,  Senior  Surgeon  to  St.  Mark's 
Hospital ;  late  Surgeon  to  the  London  Lock  Hospital,  etc.  Edited  by  Edward 
CoTTERELL,  F.R.C.S.,  Surgeon  London  Lock  Hospital,  etc.  Second  Edition. 
Enlarged  and  Illustrated  with  20  Full-Page  Plates  containing  many  handsome 
Colored  Figures.     Octavo.  Cloth,  $5.00 

COPLIN.  Manual  of  Pathology.  Including  Bacteriology,  the  Technic  of  Post- 
Mortems,  and  Methods  of  Pathologic  Research.  By  W.  M.  Late  Coplin,  m.d., 
Professor  of  Pathology  and  Bacteriology,  Jefferson  Medical  College  ;  Pathologist 
to  Jefferson  Medical  College  Hospital  and  to  the  Philadelphia  Hospital ;  Bacte- 
-  riologist  to  the  Pennsylvania  State  Board  of  Health.  Third  Edition,  Rewritten  and 
Enlarged.    275  Illustrations,  many  of  which  are  original.    i2mo.    Nearly  Ready. 

COPLIN  and  SEVAN.  Practical  Hygiene.  By  W.  M.  L.  Coplin,  m.d.,  and  D. 
Bevan,  m.d.,  Ass't  Department  of  Hygiene,  Jefferson  Medical  College;  Bac- 
teriologist, St.  Agnes'  Hospital,  Philadelphia,  with  an  Introduction  by  Prof. 
H.  A.  Hare,  and  articles  on  Plumbing,  Ventilation,  etc.,  by  Mr.  W.  P.  Locking- 
ton.     138  Illustrations.     8vo.     Second  Edition.  In  Preparation. 

CRIPPS.  Ovariotomy  and  Abdominal  Surgery.  By  Harrison  Cripps,  f.r.c.s., 
Surgical  Staff,  St.  Bartholomew's  Hospital,  London.  With  17  Plates,  several  of 
which  are  Colored  and  115  other  Illustrations.     Large  Octavo.  Cloth,  $8.00 

CROCKER.  Diseases  of  the  Skin.  Their  Description,  Pathology,  Diagnosis,  and 
Treatment,  with  special  reference  to  the  Skin  Eruptions  of  Children.  By  H. 
Radcliffe  Crocker,  m.d.,  Physician  to  the  Dept.  of  Skin  Diseases,  University 
College  Hospital,  London.     92  Illustrations.     Third  Edition.  Preparing. 

CUFF.  Lectures  on  Medicine  to  Nurses.  By  Herbert  Edmund  Cuff,  m.d.,  Late 
Ass't  Medical  Officer,  Stockwell  Fever  Hospital,  England,  Second  Edition,  Re- 
vised.    With  25  Illustrations.  Cloth,  $1.25 

CULLINGWORTH.    A  Manual  of  Nursing,  Medical  and  Surgical.    By  Charles 

J.  CuLLiNGWORTH,    M.D.,    Physician  to  St.  Thomas'  Hospital,  London.     Third 

Revised  Edition.     With  Illustrations.     i2mo.  Cloth,  .75 

A  Manual  for  Monthly  Nurses.    Third  Edition.    32mo,  Cloth,  .40 

DALBY.  Diseases  and  Injuries  of  the  Ear.  By  Sir  William  B.  Dalby,  m.d.. 
Aural  Surgeon  to  St.  George's  Hospital,  London.  Illustrated.  Fourth  Edition. 
With  38  Wood  Engravings  and  8  Colored  Plates.  Cloth,  ^2.50 

DAVIS.  A  Manual  of  Obstetrics.  Being  a  complete  manual  for  Physicians  and 
Students.  By  Edward  P.  Davis,  a.m.,  m.d..  Professor  of  Obstetrics  in  the  Jef- 
ferson Medical  College ;  Professor  of  Obstetrics  in  the  Philadelphia  Polyclinic ; 
Clinical  Professor  of  Pediatrics  in  the  Woman's  Medical  College  of  Philadelphia  ; 
Attending  Obstetrician  to  the  Philadelphia  Hospital  and  to  the  Jefferson  Hospital ; 
Member  of  the  American  Gynaecological  Society,  of  the  American  Pediatric 
Society,  of  the  International  Congress  of  Gynaecology  and  Obstetrics,  of  the 
College  of  Physicians  of  Philadelphia,  of  the  Philadelphia  Obstetrical  Society, 
etc.  Third  Edition,  Revised.  With  many  Colored  and  other  Illustrations,  a 
large  number  of  which  have  been  drawn  for  this  edition  by  a  special  artist, 
i2mo.  Preparing. 

DAVIS.    Essentials  of  Materia  Medica  and  Prescription  Writing.    By  J. 

Aubrey  Davis,  m.d.,  Ass't  Dem.  of  Obstetrics  and  Quiz  Master  in  Materia 
Medica,  University  of  Pennsylvania;  Ass't  Physician,  Home  for  Crippled  Chil- 
dren, Philadelphia.      i2mo.  $1.50 

DOMVILLE.  Manual  for  Nurses  and  others  engaged  in  attending  to  the  sick.  By 
Ed.  J.  DoMViLLE,  M.D.  Eighth  Edition.  Revised.  With  Recipes  for  Sick- 
room Cookery,  etc.     i2mo.  Cloth,  .75 

DONDERS.  Refraction.  An  Essay  on  the  Nature  and  the  Consequences  of 
Anomalies  of  Refraction.  By  F.  C.  Donders,  m.d.,  late  Professor  of  Physiology 
and  Ophthalmology  in  the  University  of  Utrecht.  Authorized  Translation. 
Revised  and  Edited  by  Charles  A.  Oliver,  a.m.,  m.d.  (Univ.  Pa.),  one  of  the 
Attending  Surgeons  to  the  Wills  Eye  Hospital ;  one  of  the  Ophthalmic  Surgeons 
to  the  Philadelphia  Hospital,  etc.  With  a  Portrait  of  the  Author  and  a  series  of 
Explanatory  Diagrams.     Octavo.     Just  Ready.  Half  Morocco,  Gilt,  Si. 25 


10  p.  BLAKISTON'S  SON  &-  CO:S 

DEAVER.  Surgical  Anatomy,  A  Treatise  on  Human  Anatomy  in  its  Application 
to  the  Practice  of  Medicine  and  Surgery.  By  John  B.  Deaver,  m.d.,  Surgeon- 
in-chief  to  the  German  Hospital;  Surgeon  to  the  Children's  Hospital,  and  to  the 
Philadelphia  Hospital ;  Consulting  Surgeon  to  St.  Agnes',  St.  Timothy's,  and  Ger- 
mantown  Hospitals;  formerly  Assistant  Professor  of  Applied  Anatomy,  University 
of  Pennsylvania,  etc.  With  about  400  very  handsome  full-page  Illustrations 
engraved  from  original  drawings  made  by  special  artists  from  dissections  pre- 
pared for  the  purpose  in  the  dissecting  rooms  of  the  University  of  Pennsylvania. 
Three  large  volumes.  Royal  square  octavo.  Sold  by  Subscription.  Orders 
taken  for  complete  sets  only.     Description  upon  Application. 

Cloth,  $21.00;  Half  Morocco  or  Sheep,  $24.00;  Half  Russia,  $27.00 
Appendicitis.  Its  History,  Anatomy,  Etiology,  Pathology,  Symptoms,  Diag- 
nosis, Prognosis,  Treatment,  Complications,  and  Sequelae.  A  Systematic 
Treatise,  with  Colored  Illustrations  of  Methods  of  Procedure  in  Operating 
and  Plates  of  Typical  Pathological  Conditions  drawn  specially  for  this  work. 
32  Full-Page  Plates.     8vo.  Cloth,  $3.50 

DUCKWORTH.  On  Gout.  Illustrated.  A  treatise  on  Gout.  By  Sir  Dyce 
Duckworth,  m.d.  (Edin.),  f.r.c.p..  Physician  to,  and  Lecturer  on  Clinical 
Medicine  at,  St.  Bartholomew's  Hospital,  London.  With  Chromo-lithograohs 
and  Engravings.     Octavo.  Cloth,  $6.00 

DtJHRSSEN.  A  Manual  of  Gynecological  Practice.  By  Dr.  A.  Duhrssen, 
Privat-docent  in  Midwifery  and  Gynecology  in  the  University  of  Berlin.  Trans- 
lated from  the  Fourth  German  Edition  and  Edited  by  John  W.  Taylor,  f.r.c.S., 
Surgeon  to  the  Birmingham  and  Midlands  Hospital  for  W^omen  ;  Vice-President 
of  the  British  Gynecological  Society ;  and  Frederick  Edge,  m.d.,  m.r.c.p., 
F.R.C.S.,  Surgeon  to  the  Wolverhampton  and  District  Hospital  for  Women.  With 
105  Illustrations.     i2mo.  Cloth,  $1.50 

DULLES.  What  to  Do  First  In  Accidents  and  Poisoning.  By  C.  W.  Dulles,  m.d. 
Fifth  Edition,  Enlarged,  with  new  Illustrations.     i2mo.  Cloth.  $1.00 

EGKLEY.  Practical  Anatomy.  Including  a  Special  Section  on  the  Fundamental 
Principles  of  Anatomy.  A  Manual  for  the  Use  of  Students  in  the  Dissecting 
Room.  Based  upon  Morris'  Text-Book  of  Anatomy.  By  W.  T.  Eckley,  m.d., 
Professor  of  Anatomy  in  the  College  of  Physicians  and  Surgeons;  Professor  of 
Anatomy  in  the  Dental  Department,  Northwestern  University,  Chicago,  etc., 
and  Corrinne  Buford  Eckley,  Professor  of  Anatomy  in  the  Northwestern 
University  Women's  Medical  School ;  Professor  of  Anatomy  in  the  Chicago 
School  of  Anatomy  and  Physiology,  etc.  With  340  Illustrations,  many  of  which 
are  colored.     Octavo.  Cloth,  $3.50  ;  Water-Proof,  $4.00 

FEMWICK,    Guide  to  Medical  Diagnosis.    By  Samuel  Fenwick,  m.d.,  f.r.c.p., 

Consulting  Physician  to  the  London  Hospital;  and  W.  S.  Fenwick,  m.d., 
M.R.C.P.,  Physician  to  the  Out- Patients,  Evelina  Hospital  for  Children.  Eighth 
Edition.     In  great  part  rewritten,  with  several  new  chapters.     135  Illustrations. 

Cloth,  $2.50 

FICK.  Diseases  of  the  Eye  and  Ophthalmoscopy.  A  Handbook  for  Physicians 
and  Students.  By  Dr.  Eugen  Fick,  University  of  Zurich.  Authorized  Transla- 
tion by  A.  B.  Hale,  m.d..  Ophthalmic  Surgeon,  United  Hebrew  Charities  ;  Con- 
sulting Ophthalmic  Surgeon,  Charity  Hospital,  Chicago;  late  Vol.  Assistant, 
Imperial  Eye  Clinic,  University  of  Kiel.  With  a  Glossary  and  158  Illustrations, 
many  of  which  are  in  colors.  Bvo.    Cloth,  $4.50 ;  Sheep,  $5.50 ;  Half  Russia,  $6.50 

FIELD.  Evacuant  Medication — Cathartics  and  Emetics.  By  Henry  M.  Field, 
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ber Gynaecological  Society  of  Boston,  etc.     i2mo.     288  pp.  Cloth,  $1.75 

FILLEBROWN.  A  Text-Book  of  Operative  Dentistry.  Written  by  invitation 
of  the  National  Association  of  Dental  Faculties.  By  Thomas  Fillebrown,  m.d., 
D.M.D.,  Professor  of  Operative  Dentistry  in  the  Dental  School  of  Harvard  Uni- 
versity ;  Member  of  the  American  Dental  Assoc,  etc.    Illus.    8vo.     Clo.    $2.25 

FOWLER'S  Dictionary  of  Practical  Medicine.  By  Various  Writers.  An  Ency- 
clopedia of  Medicine.  Edited  by  James  Kingston  Fowler,  m.a.,  m.d.,  f.r.c.p., 
Senior  Asst.  Physician  to,  and  Lecturer  on  Pathological  Anatomy  at,  the  Mid- 
dlesex Hospital,  London.     8vo.  Cloth,  $3.00;  Half  Morocco,  $4.00 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  11 

PULLERTON.  Obstetric  Nursing.  By  Anna  M.  Fullertox,  m.d„  Demon- 
strator of  Obstetrics  in  the  Woman's  Medical  College ;  Obstetrician  and 
Gynecologist  to  the  Woman's  Hospital,  Philadelphia,  etc.  41  Illustrations. 
Fifth  Edition.    Revised  and  Enlarged.   i2mo.  Cloth,  gi.co 

Surgical  Nursing.  Comprising  the  Regular  Course  of  Lectures  upon 
Abdominal  Surgery,  Gynecology,  and  General  Surgical  Conditions  delivered 
at  the  Training  School  of  the  Woman's  Hospital,  Philadelphia.  Third 
Edition,  Revised.     69  Illustrations.     i2mo.  Cloth,  $1.00 

CrARDNER.    The  Brewer,  Distiller  and  Wine  Manufacturer.    A  Handbook  for 

all  Interested  in  the  Manufacture  and  Trade  of  Alcohol  and  Its  Compounds. 

Edited  by  John  Gardner,  f.c.s.     Illustrated.  Cloth,  $1.50 

Bleaching,  Dyeing,  and  Calico  Printing.  With  Formulae.    Illustrated.     $1.50 

QARROD.  On  Rheumatism.  A  Treatise  on  Rheumatism  and  Rheumatic  Arthritis. 
By  Archibald  Edward  Garrod,  m.a.  (Oxon.),  m.d.,  m.r.c.s.  (Eng.),  Asst. 
Physician,  West  London  Hospital.     Illustrated.     Octavo.  Cloth,  ^5.00 

GILLIAM'S  Pathology.  The  Essentials  of  Pathology;  a  Handbook  for  Students. 
By  D.  Tod  Gilliam,  m.d.,  Professor  of  Physiology,  Starling  Medical  College, 
Columbus,  O.    With  47  Illustrations.    i2mo.  Cloth,  .75 

GOODALL    and    WASHBOURN.     A  Manual  of  Infectious   Diseases.     By 

Edward  W.  Goodall,  m.d.  (London),  Medical  Superintendent  Eastern  (Fever) 
Hospital,  Homerton,  London,  etc.,  and  J.  W.  Washbourn,  f.r.c.p.,  Assistant 
Physician  to  Guy's  Hospital  and  Physician  to  the  London  Fever  Hospital. 
Illustrated  with  Charts,  Diagrams,  and  Full-Page  Plates.  Cloth,  $3.00 

GOULD.    The  Illustrated  Dictionary  of  Medicine,  Biology,  and  Allied  Sciences. 

Being  an  Exhaustive  Lexicon  of  Medicine  and  those  Sciences  Collateral  to  it, 
Biology  (Zoology  and  Botany),  Chemistry,  Dentistry,  Pharmacology,  Microscopy  : 
etc.     By  George  M.  Gould,  m.d..  Editor  of  The  Philadelphia  Medical  Journal  ; 
President,  1893-94,  American  Academy  of  Medicine,  etc.     With  many  Useful 
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Pronunciation  and  Definitions,  based  on  Recent  Medical  Literature.     With 
Tables  of  the  Bacilli,  Micrococci,  Leucomains,  Ptomains,  etc.,  of  the  Arteries, 
Muscles,  Nerves,  Ganglia  and  Plexuses;  Mineral  Springs  of  U.  S.,  etc.    Re- 
written, Enlarged,  and  set  from  new  Type.     Small  octavo,  700  pages. 

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Medical  Lexicon.  Containing  all  the  Words,  their  Definition  and  Pronun- 
ciation, that  the  Student  generally  comes  in  contact  with;  also  elaborate 
Tables  of  the  Arteries,  Muscles,  Nerves,  Bacilli,  etc.,  etc. ;  a  Dose  List  in  both 
English  and  Metric  Systems,  a  new  table  of  Clinical  Eponymic  Terms,  etc., 
arranged  in  a  most  convenient  form  for  reference  and  memorizing.  A  new 
edition,  completely  revised  and  set  from  new  type.  225  pages  new  material. 
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and  Thought.    By  George  M.  Gould,  m.d.    350  pages.    i2mo.    Cloth,  $2.00 

Compend  of  Diseases  of  the  Eye  and  Refraction.  Including  Treatment 
and  Operations,  with  a  Section  on  Local  Therapeutics.  By  George  M. 
Gould,  m.d.,  and  W.  L.  Pyle,  m.d.  With  Formulas,  Glossary,  and  several 
Tables.  Second  Edition.  109  Illustrations,  several  of  which  are  Colored. 
No.  8  f  Quis- Compend f  Series.        Cloth,  .80.     Interleaved  for  Notes,  51.25 


12  P.  BLAKISTON'S  SON  &-  CO.'S 

GORDINIER.  The  Gross  and  Minute  Anatomy  of  the  Central  Nervous 
System.  By  H.  C.  Gordinier,  a.m.,  m.d.,  Professor  of  Physiology  and  of  the 
Anatomy  of  the  Nervous  System  in  the  Albany  Medical  College ;  Member 
American  Neurological  Association.  With  48  full-page  Plates  and  213  other 
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original.  Large  8vo.  Handsome  Cloth,  $6.00;  Sheep,  $7.00;  Half  Russia,  $8.00 
GORGAS'S  Dental  Medicine.  A  Manual  of  Materia  Medica  and  Therapeutics. 
By  Ferdinand  J.  S.  Gorgas,  m.d.,  d.d.S.,  Professor  of  the  Principles  of  Dental 
Science,  Oral  Surgery  and  Dental  Mechanism  in  the  Dental  Dep.  of  the  Univ. 
of  Maryland.    Sixth  Edition.    Revised  and  Enlarged,  with  many  Formulce.    8vo. 

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GRIFFITH'S  Graphic  Clinical  Chart.    Designed  by  J.  P.  Crozer  Griffith, 
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GROFF.    Materia  Medica  for  Nurses.    With  Questions  for  Self-Examination 
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GROVES  and  THORP.    Chemical  Technology.    A  new  and  Complete  Work. 
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GOWERS.  Manual  of  Diseases  of  the  Nervous  System.  A  Complete  Text-book. 

By  William  R.  Gowers,  m.d.,  f.r.s..  Physician  to  National  Hospital  for  the 

Paralyzed  and  Epileptic;    Consulting  Physician,  University  College   Hospital; 

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Syphilis  and  the  Nervous  System.  Being  a  revised  reprint  of  the  Lettso- 
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Diagnosis  of  Diseases  of  the  Brain.  8vo.  Second  Ed.  lUus.  Cloth,  $1.50 
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changes  of  the  Eye  in  Diseases  of  the  Brain,  Kidney,  etc.  Third  Edition. 
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matism, Diabetes,  Bright's  Disease,  Anaemia,  etc.  By  Alex.  Haig,  m.a.,  m.d. 
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MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  13 

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HALL.  Compend  of  General  Pathology  and  Morbid  Anatomy.  By  H.  Newbery 

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Chicago.     91  lUus.     2d  Edition.     No.  i§  fQuiz-Compend?  Series.       Preparing. 

HALL.  Diseases  of  the  Nose  and  Throat.  By  F.  De  Havilland  Hall,  m.d., 
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HANSELL  and  EEBER.  Muscular  Anomalies  of  the  Eye.  By  Howard  F. 
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College;  Professor  of  Diseases  of  the  Eye,  Philadelphia  Polyclinic,  etc.,  and 
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HARLAN.    Eyesight,  and  How  to  Care  for  It.    By  George  C.  Harlan,  m.d., 
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HARRIS'S  Principles  and  Practice  of  Dentistry.    Including  Anatomy,  Physi- 
ology, Pathology,  Therapeutics,  Dental  Surgery  and  Mechanism.     By  Chapin  A. 
Harris,  m.d.,  d.d.s.,  late  President  of  the  Baltimore  Dental  College,  Author  of 
"  Dictionary  of  Medical  Terminology  and  Dental  Surgery."     Thirteenth  Edition. 
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tal for  Diseases  of  the  Chest ;  Examining  Physician  to  the  Royal  National  Hos- 
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tholomew's Hospital,  etc.  104  Illustrations  and  Sheet  of  Test  Types.  Ninth 
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HARTSHORNE.  Our  Homes.  Their  Situation,  Construction,  Drainage,  etc.  By 
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HATFIELD.  Diseases  of  Children.  By  Marcus  P.  Hatfield,  Professor  of 
Diseases  of  Children,  Chicago  Medical  College.  With  a  Colored  Plate.  Second 
Edition.     Being  No.  14,  ?  Quiz- Compend?  Series.     i2mo.  Cloth,  .80 

Interleaved  for  the  addition  of  notes,  ^1.25 


14  P.  BLAKISTON'S  SON  <S-  CO.'S 

HELLER.  Essentials  of  Materia  Medica,  Pharmacy,  and  Prescription  Writ- 
ing. By  Edwin  A.  Heller,  m.d.,  Quiz-Master  in  Materia  Medica  and  Phar- 
macy at  the  Medical  Institute,  University  of  Pennsylvania.    i2mo.     Cloth,  $1.50 

HEATH.    Minor  Surgery  and  Bandaging.    By  Christopher  Heath,  f.r.c.s,, 

Holme  Professor  of  Clinical  Surger}'  in  University  College,  London.     Eleventh 

Edition.      Revised  and   Enlarged.     With   158    Illustrations,  62  Formulae,  Diet 

List,  etc.     i2mo.  Cloth,  $1.25 

Practical  Anatomy.      A  Manual  of  Dissections.      Eighth  London  Edition. 

300  Illustrations.  Cloth,  $4.25 

Injuries  and  Diseases  of  the  Jaws.    Fourth  Edition.    Edited  by  Henry 

Percy   Dean,    m.s.,  f.r.c.s.,  Assistant   Surgeon    London  Hospital.     With 

187  Illustrations.    Bvo.  Cloth,  $4.50 

Lectures  on  Certain  Diseases  of  the  Jaws,  delivered  at  the  Royal  College  of 
Surgeons  of  England,  1887.     64  Illustrations.     8vo.  Boards,  .50 

HEMMETER.  Diseases  of  the  Stomach.  Their  Special  Pathology,  Diagnosis, 
and  Treatment.  With  Sections  on  Anatomy,  Analysis  of  Stomach  Contents, 
Dietetics,  Surgery  of  the  Stomach,  etc.  By  John  C.  Hemmeter,  m.d.,  philos.d., 
Clinical  Professor  of  Medicine  in  the  University  of  Maryland  ;  Consultant  to  the 
University  Hospital;  Director  of  the  Clinical  Laboratory,  etc.;  formerly  Clini- 
cal Professor  of  Medicine  at  the  Baltimore  Medical  College,  etc.  Second 
Edition,  thoroughly  revised  and  in  parts  rewritten.  With  Colored  and  other 
Illustrations.  Cloth,  $6.00;  Leather,  $7.00  ;  Half  Russia,  $8.00 

HENRY.  Anaemia.  A  Practical  Treatise.  By  Fred'k  P.  Henry,  m.d..  Physician 
to  Episcopal  Hospital,  Philadelphia.  Half  Cloth,  .50 

HEWLETT.  Manual  of  Bacteriology.  By  R.  T.  Hewlett,  m.d.,  m.r.c.p.,  Asst. 
Bacteriologist  British  Institute  of  Preventive  Medicine,  etc.  With  75  Illustra- 
tions.    Octavo.  Cloth,  $3.00 

HOLLOPETER.  Hay  Fever  and  Its  Successful  Treatment.  By  W.  C.  Hollo- 
peter,  A.M.,  M.D.,  Clinical  Professor  of  Pediatrics  in  the  Medico- Chirurgical  Col- 
lege of  Philadelphia,  Physician  to  the  Methodist  Episcopal,  Medico-Chirurgical, 
and  St.  Joseph  Hospitals,  etc.     Second  Edition,  Enlarged.    i2mo.      Cloth,  $1.00 

HOLDEN'S  Anatomy.  Seventh  Edition.  A  Manual  of  the  Dissections  of  the  Human 
Body.  By  John  Langton,  f.r.c.s..  Surgeon  to,  and  Lecturer  on  Anatomy  at, 
St.  Bartholomew's  Hospital.  Carefully  Revised  by  A.  Hewson,  m.d.,  Demonstra- 
tor of  Anatomy,  Jefferson  Medical  College,  etc.  311  Illustrations.  i2mo.  800 
pages.  Preparing. 

Human  Osteology.  Comprising  a  Description  of  the  Bones,  with  Colored 
Delineations  of  the  Attachments  of  the  Muscles.  The  General  and  Micro- 
scopical Structure  of  Bone  and  its  Development.  8th  Ed.,  carefully  Revised. 
W^ith  Lithographic  Plates  and  Numerous  Illustrations.  Cloth,  $5.25 

Landmarks.     Medical  and  Surgical.     4th  Edition.     8vo.  Cloth,  Ji.oo 

HOLLAND.  The  Urine,  the  Gastric  Contents,  the  Common  Poisons  and  the 
Milk.  Memoranda,  Chemical  and  Microscopical,  for  Laboratory  Use.  By  J.  W. 
Holland,  m.d.,  Professor  of  Medical  Chemistry  and  Toxicology  in  Jeflferson 
Medical  College,  of  Philadelphia.  Fifth  Edition,  Enlarged.  Illustrated  and 
Interleaved.  i2mo.  Cloth,  $1.00 

HORWITZ'S  Compend  of  Surgery,  including  Minor  Surgery,  Amputations,  Frac- 
tures, Dislocations,  Surgical  Diseases,  and  the  Latest  Antiseptic  Rules,  etc.,  with 
Differential  Diagnosis  and  Treatment.  By  Orville  Horwitz,  b.s.,  m.d.,  Pro- 
fessor of  Genito-Urinary  Diseases,  late  Demonstrator  of  Surgery,  Jefferson  Medi- 
cal College.  Fifth  Edition.  Very  much  Enlarged  and  Rearranged.  Over  300 
pages.     167  Illustrations  and  98  Formulae.    i2mo.  No.  g  ? Quiz- Compend  f  Series. 

Cloth,  .80.     Interleaved  for  notes,  JiSi.25 
*^*  A  Spanish  translation  of  this  book  has  recertify  been  published  in  Barcelona. 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  15 

HORSLEY.  The  Brain  and  Spinal  Cord.  The  Structure  and  Functions  of.  By 
Victor  A.  Horsley,  m.b.,  f.r.s.,  etc.,  Asst.  Surg.,  University  College  Hospital, 
London,  etc.     Illustrated.  Cloth,  $2.50 

HOVELL.    Diseases  of  the  Ear  and  Naso-Pharynx.     A  Treatise  including 

Anatomy  and  Physiology  of  the  Organ,  together  with  the  treatment  of  the  affec- 
tions of  the  Nose  and  Pharynx  which  conduce  to  aural  disease.  By  T.  Mark 
HovELL,  F.R.c.s.  (Edin.),  m.r.c.s.  (Eng.),  Aural  Surgeon  to  the  London  Hospital, 
for  Diseases  of  the  Throat,  etc.      122  lUus.     Second  Edition.  Preparing. 

HUMPHREY.  A  Manual  for  Nurses.  Including  general  Anatomy  and  Physiology, 
management  of  the  sick-room,  etc.  By  Laurence  Humphrey,  m.'a.,  m.b., 
M.R.C.S.,  Assistant  Physician  to,  and  Lecturer  at,  Addenbrook's  Hospital,  Cam- 
bridge, England.     Sixteenth  Edition.     i2mo.     Illustrated.  Cloth,  $1.00 

HUGHES.  Compend  of  the  Practice  of  Medicine.  Sixth  Edition.  Revised  and 
Enlarged.  By  Daniel  E.  Hughes,  m.d..  Chief  Resident  Physician  Philadelphia 
Hospital ;  formerly  Demonstrator  of  Chnical  Medicine  at  Jefferson  Medical  Col- 
lege, Philadelphia.  In  two  parts.  Being  Nos.  2  and ^,  ? Quiz- Compend?  Series. 
Part  I. — Continued,  Eruptive  and  Periodical  Fevers,  Diseases  of  the  Mouth, 
Stomach,  Intestines,  Peritoneum,  Biliary  Passages,  Liver,  Kidneys,  Blood,  etc., 
Parasites,  etc.,  and  General  Diseases,  etc. 

Part  II. — Physical  Diagnosis,  Diseases  of  the  Respiratory  System,  Circulatory 
System,  Diseases  of  the  Brain  and  Nervous  System,  Mental  Diseases,  etc. 

Price  of  each  Part,  in  Cloth,  .80  ;  interleaved  for  the  addition  of  Notes,  $1.25 
Physicians'  Edition. — In  one  volume,  including  the  above  two  parts,  a  sec- 
tion on  Skin  Diseases,  and  an  index.     Sixth  revised  and  enlarged  Edition. 
62^  pages.  Full  Morocco,  Gilt  Edge,  Round  Corners,  $2.25 

"  Carefully  and  systematically  compiled." — The  London  Lancet. 

HUTCHINSON.  The  Nose  and  Throat.  A  Manual  of  the  Diseases  of  the  Nose 
and  Throat,  including  the  Nose,  Naso-Pharynx,  Pharynx  and  Larynx.  By 
Procter  S.  Hutchinson,  m.r.c.s.,  Ass't  Surgeon  to  the  London  Hospital  for 
Diseases  of  the  Throat.  Illustrated  by  Lithograph  Plates  and  40  other  Illus., 
many  of  which  have  been  made  from  original  drawings.    i2mo.   2d  Ed.    In  Press. 

IMPEY.  A  Handbook  on  Leprosy.  By  S.  P.  Impey,  m.d.,  m.c.  Late  Chief  and 
Medical  Superintendent,  Robben  Island  Leper  and  Lunatic  Asylums,  Cape  Col- 
ony, South  Africa.     Illustrated  by  37  Plates  and  a  Map.     Octavo.      Cloth,  I3.50 

JACOBSON.     Operations  of  Surgery.     By  W.  H,  A.  Jacobson,  b.a.  (Oxon.), 

F.R.c.s.,  (Eng.);  Ass't  Surgeon,  Guy's  Hospital;    Surgeon  at  Royal  Hospital  for 

Children  and  Women,  etc.     With  over  200  lUust.      Cloth,  ^3.00  ;  Leather,  S4.00 

Diseases  of  the  Male  Organs  of  Generation.    88  Illustrations.    Cloth,  $6.00 

JESSOP.  Manual  of  Ophthalmic  Surgery  and  Medicine.  By  Walter  H.  H. 
Jessop,  m.b.  (Cantab.),  f.r.c.s..  Ophthalmic  Surgeon  to  and  Lecturer  on  Oph- 
thalmic Medicine  and  Surgery  at  St.  Bartholomew's  Hospital,  London.  With 
5  Colored  Plates,  Test  Types,  and  no  other  Illustrations.     i2mo.       Cloth,  S3-oo 

JONES.  Medical  Electricity.  A  Practical  Handbook  for  Students  and  Prac- 
titioners of  Medicine.  By  H.  Lewis  Jones,  m.a.,  m.d.,  m.r.c.p..  Medical  Officer 
in  Charge  Electrical  Department,  St.  Bartholomew's  Hospital.  Third  Edition 
of  Steavenson  and  Jones'  Medical  Electricity.  Revised  and  Enlarged.  112  Illus- 
trations.    i2mo.  Preparing. 

KEEN.  Clinical  Charts.  A  series  of  seven  Outline  Drawings  of  the  Human  Body, 
on  which  may  be  marked  the  course  of  any  Disease,  Fractures,  Operations,  etc. 
By  W.  W.  Keen,  m.d..  Professor  of  the  Principles  of  Surgery  and  Clinical  Sur- 
gery, Jefferson  Medical  College,  Philadelphia.  Put  up  in  pads  of  50,  with 
explanations.  Each  pad,  $1.00.  Each  Drawing  may  also  be  had  separately 
gummed  on  back  for  pasting  in  case  book.     25  to  the  pad.     Price,  25  cents. 

*^*  Special  Charts  will  be  printed  to  order.     Samples  free. 


16  P.  BLAKISTON'S  SON  6-  CO:S 

KIHKE'S  Physiology.  {15^^  Authorized  Edition.  i2mo.  Dark  Red  Cloth.) 
A  Handbook  of  Physiology.  Fifteenth  London  Edition,  Revised  and  Enlarged. 
By  W.  D.  Halliburton,  m.d.,  f.r.s..  Professor  of  Physiology  King's  College, 
London.  Thoroughly  Revised  and  in  many  parts  Rewritten.  668  lllus.,  many 
of  which  are  printed  in  Colors.    872  pages.     i2mo.    Cloth,  $3.cxd  ;   Leather,  $3.75 

IMPORTANT   NOTICE.     This  is  the  identical  Edition  of  "  Kirke's  Physiology,"  as  published 

in   London  by  John   Murray,  the  sole  owner  of  the  book.     It  is  the 

only  edition  containing  the  revisions  and  additions  of  Dr.  Halliburton,  and  the  new  and  original 
illustrations  included  at  his  suggestion.     This  edition  has  been  carefully  and  thoroughly  revised. 

KENWOOD.    Public  Health  Laboratory  Work.     By  H.  R.  Kenwood,  m.b., 

D.P.H.,  F.C.S.,  Instructor  in  Hygienic  Laboratory,  University  College,  late  Assistant 
Examiner  in  Hygiene,  Science  and  Art  Department,  South  Kensington,  London, 
etc.     With  116  Illustrations  and  3  Plates.  Cloth,  $2.00 

KLEEN.  Handbook  of  Massage.  By  Emil  Kleen,  m.d.,  ph.d.,  Stockholm  and 
Carlsbad.  Authorized  Translation  from  the  Swedish,  by  Edward  Mussey  Hart- 
well,  m.d.,  PH.D.,  Director  of  Physical  Training  in  the  Public  Schools  of  Boston, 
With  an  Introduction  by  Dr.  S.  Weir  Mitchell,  of  Philadelphia.  Illustrated 
by  Photographs  made  specially  for  the  American  Edition.     8vo.         Cloth,  ^2.25 

KNOPF.  Pulmonary  Tuberculosis :  Its  Modern  Prophylaxis  and  the  Treat- 
ment in  Special  Institutions  and  at  Home.  By  S.  A.  Knopf,  m.d..  Physician 
to  the  Lung  Department  of  the  New  York  Throat  and  Nose  Hospital ;  former 
Assistant  Physician  to  Prof.  Dettweiler,  Falkenstein  Sanatorium,  Germany,  etc. 
Illustrated.     Octavo.  Cloth,  $3.00 

LANDIS'  Compend  of  Obstetrics  ;  especially  adapted  to  the  Use  of  Students  and 
Physicians.  By  Henry  G.  Landis,  m.d.  Sixth  Edition.  Revised  by  Wm.  H. 
Wells,  m.d..  Instructor  of  Obstetrics,  Jefferson  Medical  College;  Member 
Obstetrical  Society  of  Philadelphia,  etc.  With  47  Illustrations.  No.^  ?  Quiz- 
Covipendf  Series.  Cloth,  .80;  interleaved  for  the  addition  of  Notes,  ^1.25 

LANDOIS.  A  Text-Book  of  Human  Physiology  ;  including  Histology  and  Micro- 
scopical Anatomy,  with  special  reference  to  the  requirements  of  Practical  Medi- 
cine. By  Dr.  L.  Landois,  Professor  of  Physiology  and  Director  of  the  Physio- 
logical Institute  in  the  University  of  Greifswald.  Fifth  American,  translated 
from  the  last  German  Edition,  with  additions,  by  Wm.  Stirling,  m.d.,  d.Sc, 
Brackenbury  Professor  of  Physiology  and  Histology  in  Owen's  College,  and  Pro- 
fessor in  Victoria  University,  Manchester  ;  Examiner  in  Physiology  in  University 
of  Oxford,  England.  With  845  Illustrations,  many  of  which  are  printed  in 
Colors.     8vo.  In  Press. 

LANE.  Surgery  of  the  Head  and  Neck.  By  L.  C.  Lane,  a.m.,  m.d.,  m.r.c.s. 
(Eng.),  Professor  of  Surgery  in  Cooper  Medical  College,  San  Francisco.  Second 
Edition,  with  no  Illustrations.     Octavo.  Cloth,  $5.00 

LAZARUS-BARLOW.    General  Pathology.    By  W.  S.  Lazarus-Barlow,  m.d., 
Demonstrator  of  Pathology  at  the  University  of  Cambridge,  England. 
795  pages.     Octavo.  Cloth,  $5.00 

LEE.  The  Microtomist's  Vade  Mecum.  Fourth  Edition.  A  Handbook  of 
Methods  of  Microscopic  Anatomy.  By  Arthur  Bolles  Lee,  formerly  Ass't  in 
the  Russian  Laboratory  of  Zoology,  at  Villefranche-sur-Mer  (Nice).  887  Articles. 
Enlarged  and  Revised,  and  in  many  portions  greatly  extended.    8vo.   Cloth,  $4.00 

LEFFMANN'S  Compend  of  Medical  Chemistry,  Inorganic  and  Organic.  In- 
cluding Urine  Analysis.  By  Henry  Leffmann,  m.d.,  Prof,  of  Chemistry  in 
the  Woman's  Medical  College  in  the  Penna.  College  of  Dental  Surgery  and 
in  the  Wagner  Free  Institute  of  Science,  Philadelphia ;  Pathological  Chemist 
Jefferson  Medical  College.  No.  10  ? Quiz- Co7)ip end  f  Series.  Fourth  Edition. 
Rewritten.  Cloth,  .80.    Interleaved  for  the  addition  of  Notes,  %\.i^ 

The  Coal-Tar  Colors,  with  Special  Reference  to  their  Injurious  Qualities  and 
the  Restrictions  of  their  Use.  A  Translation  of  Theodore  Weyl's  Mono- 
graph.    i2mo.  Cloth,  %\.i'^ 

Examination  of  Water  for  Sanitary  and  Technical  Purposes.  Fourth  Edition. 
Enlarged.     Illustrated.     i2mo.  Cloth,  J51.25 


MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  17 

LEFFMANN'S  Analysis  of  Milk  and  Milk  Products.    Arranged  to  suit  the  needs 

of   Analytical    Chemists,    Dairymen,    and    Milk    Inspectors.     Second   Edition, 

Revised  and  Enlarged,  with  Illustrations.     i2mo.  Cloth,  $1.25 

Handbook  of  Structural  Formulae  for  the  Use  of  Students,  containing  180 

Structural  and  Stereo-chemic  Formulae.     i2mo.    Interleaved.     Cloth,  $1.00 

LEWERS.    On  the  Diseases  of  Women.    A  Practical  Treatise.    By  Dr.  A.  H. 

N.  Lewers,  Assistant  Obstetric  Physician  to  the  London  Hospital ;  and  Phy- 
sician to  Out-patients,  Queen  Charlotte's  Lying-in  Hospital;  Examiner  in  Mid- 
wifery and  Diseases  of  Women  to  the  Society  of  Apothecaries  of  London.  With 
146  Engravings.     Fifth  Edition,  Revised.  Cloth,  $2.50 

LEWIS  (BEVAN).     Mental  Diseases.  A  text-book  having  special  reference  to  the 
Pathological  aspects  of  Insanity.     By  Bevan  Lewis,   l.r.c.p.,  m.r.c.s.,  Medi- 
cal Director,  West  Riding  Asylum,  Wakefield,  England.     26  Lithograph  Plates 
and  other  Illustrations.     Second  Ed.,  Revised  and  Enlarged.    8vo.     Cloth,  $7.00 
LINCOLN.    School  and  Industrial  Hygiene.    By  D.  F.  Lincoln,  m.d.    Cloth,  .40 
LIZARS  (JOHN).     On  Tobacco.     The  Use  and  Abuse  of  Tobacco.  Cloth,  .40 

LONGLEY'S  Pocket  Medical  Dictionary.  Giving  the  Definition  and  Pronuncia- 
tion of  Words  and  Terms  in  General  Use  in  Medicine,  with  an  Appendix,  con- 
taining Poisons  and  their  Antidotes,  Abbreviations  Used  in  Prescriptions,  etc. 
By  Elias  Longley.  Cloth,  .75  ;  Tucks  and  Pocket,  $1.00 

MACALISTER'S  Human  Anatomy.  800  Illustrations.  Systematic  and  Topo- 
graphical, including  the  Embryology,  Histology  and  Morphology  of  Man.  With 
special  reference  to  the  requirements  of  Practical  Surgery  and  Medicine.  By 
Alex.  Macalister,  m.d.,  f.r.s.,  Professor  of  Anatomy  in  the  University  of  Cam- 
bridge, England.     816  Illustrations.     Octavo.  Cloth,  ^5.00;  Leather,  $6.co 

MACKENZIE.  The  Pharmacopoeia  of  the  London  Hospital  for  Diseases  of 
the  Throat.  By  Sir  Morell  Mackenzie,  m.d.  Fifth  Edition.  Revised  and 
Improved  by  F.  G.  Harvey,  Surgeon  to  the  Hospital.  Cloth,  $1.00 

MACREADY.  A  Treatise  on  Ruptures.  By  Jonathan  F.  C.  H.  Macready, 
F.R.C.S.,  Surgeon  to  the  Great  Northern  Central  Hospital ;  to  the  City  of  London 
Hospital  for  Diseases  of  the  Chest ;  to  the  City  of  London  Truss  Societ}^  etc. 
With  24  full-page  Plates  and  numerous  Wood-Engravings.  Octavo.     Cloth,  $6.00 

MANN.  Forensic  Medicine  and  Toxicology.  A  Text-Book  by  J.  Dixon  Mann, 
M.D.,  F.R.C.P.,  Professor  of  Medical  Jurisprudence  and  Toxicology  in  Owens  Col- 
lege, Manchester ;  Examiner  in  Forensic  Medicine  in  University  of  London,  etc. 
Illustrated.     Octavo.  Cloth,  $6.50 

MANN'S  Manual  of  Psychological  Medicine  and  Allied  Nervous  Diseases.  Their 
Diagnosis,  Pathology,  Prognosis  and  Treatment,  including  their  Medico-Legal 
Aspects  ;  with  chapter  on  Expert  Testimony,  and  an  abstract  of  the  laws  relating 
to  the  Insane  in  all  the  States  of  the  Union.  By  Edward  C.  Mann,  m.d. 
With  Illustrations.     Octavo.  Cloth,  $3.00 

MARSHALL'S  Physiological  Diagrams,  Life  Size,  Colored.  Eleven  Life-size 
Diagrams  (each  7  feet  by  3  feet  7  inches).  Designed  for  Demonstration  before 
the  Class.  By  John  Marshall,  f.r.s.,  f.r.c.s..  Professor  of  Anatomy  to  the 
Royal  Academy  ;  Professor  of  Surgery,  University  College,  London,  etc. 

In  Sheets,  $40.00     Backed  with  MusHn  and  Mounted  on  Rollers,  $60.00 
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No.  I — The  Skeleton  and  Ligaments.  No.  2 — The  Muscles  and  Joints,  with 
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No.  4 — The  Heart  and  Principal  Blood-vessels.  No.  5 — The  Lymphatics  or  Absorb- 
ents. No.  6 — The  Digestive  Organs.  No.  7 — The  Brain  and  Nerves.  Nos.  8  and  9 — 
The  Organs  of  the  Senses.  Nos.  10  and  11 — The  Microscopic  Structure  of  the 
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MARSHALL.  The  Woman's  Medical  CoUege  of  Pennsylvania.  An  Historical 
Outline.    By  Clara  Marshall,  m.d..  Dean  of  the  College.     8vo.     Cloth,  $1.50 


18  P.  BLAKISTON'S  SON  <S-  CO:S 

MASON'S  Compend  of  Electricity,  and  its  Medical  and  Surgical  Uses.  By 
Charles  F.  Mason,  m.d.,  Assistant  Surgeon  U.  S.  Army.  With  an  Intro- 
duction by  Charles  H.  May,  m.d.,  Instructor  in  the  New  York  Polyclinic. 
Numerous  Illustrations.     i2mo.  Cloth,  .75 

MAXWELL.  Terminologia  Medica  Polyglotta.  By  Dr.  Theodore  Maxwell, 
assisted  by  others  in  various  countries.     8vo.  Cloth,  $3.00 

The  object  of  this  work  is  to  assist  the  medical  men  of  any  na'tionality  in  reading  medical  literature  written 
in  a  language  not  their  own.  Each  term  is  usually  given  in  seven  languages,  viz.  :  English,  French,  German, 
Italian,  Spanish,  Russian  and  Latin. 

MAYLAED.  The  Surgery  of  the  Alimentary  Canal.  By  Alfred  Ernest 
Maylard,  M.B.,  B.S.,  Senior  Surgeon  to  the  Victoria  Infirmary,  Glasgow.  With 
27  Full-Page  Plates  and  117  other  Illustrations.     Octavo.  Cloth,  $7.50 

MAYS'  Theine  in  the  Treatment  of  Neuralgia.  By  Thomas  J.  Mays,  m.d. 
i6mo.  Yz  bound,  .50 

McSEIDE.  Diseases  of  the  Throat,  Nose  and  Ear.  A  Clinical  Manual  for  Stu- 
dents and  Practitioners.  By  P.  McBride,  m.d.,  f.r.c.p.  (Edin.),  Surgeon  to  the 
Ear  and  Throat  Department  of  the  Royal  Infirmary;  Lecturer  on  Diseases  of 
Throat  and  Ear,  Edinburgh  School  of  Medicine,  etc.  With  Colored  Illustrations 
from  Original  Drawings.    2d  Edition.    Octavo.       Handsome  Cloth,  Gilt  top,  $6.00 

McNEILL.  The  Prevention  of  Epidemics  and  the  Construction  and  Man- 
agement of  Isolation  Hospitals.  By  Dr.  Roger  McNeill,  Medical  Officer  of 
Health  for  the  County  of  Argyll.  With  numerous  Plans  and  other  Illustrations. 
Octavo.  Cloth,  $3.50 

MEIGS.  Milk  Analysis  and  Infant  Feeding.  A  Treatise  on  the  Examination  of 
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Diet  of  Young  Infants.     By  Arthur  V.  Meigs,  m.d.     i2mo.  Cloth,  .50 

MEMMINGER.  Diagnosis  by  the  Urine.  The  Practical  Examination  of  Urine, 
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of  Chemistry  and  Hygiene ;  Clinical  Professor  of  Urinary  Diagnosis  in  the 
Medical  College  of  the  State  of  South  Carolina ;  Visiting  Physician  in  the 
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24  Illustrations.    i2mo.  Cloth,  $1.00 

MORRIS.  Text-Book  of  Anatomy.  Second  Edition.  790  Illustrations,  many 
in  Colors.  A  complete  Text-book.  Edited  by  Henry  Morris,  f.r.c.S.,  Surg, 
to,  and  Lect.  on  Anatomy  at,  Middlesex  Hospital,  assisted  by  J.  Bland  Sutton, 
F.R  C.S.,  J.  H.  Davies-Colley,  f.r.c.S.,  Wm.  J.  Walsham,  f.r.c.s.,  H.  St.  John 
Brooks,  m.d.,  R.  Marcus  Gunn,  f.r.c.s.,  Arthur  Hensman,  f.r.c.s.,  Frederick 
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Record,  New  York. 

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Renal  Surgery.  With  Special  Reference  to  Stone  in  the  Kidney  and  Ureter, 
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Examination  of  Subparietal  Injuries  of  the  Ureter.     lUustrated.     8vo. 

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MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  19 

MORTON  on  Refraction  of  the  Eye.  Its  Diagnosis  and  the  Correction  of  its  Errors. 
With  Chapter  on  Keratoscopy,  and  Test  Types.  By  A.  Morton,  m.b.  Sixth 
Edition,  Revised  and  Enlarged.  Cloth,  $i.oo 

MOULLIN.  Surgery.  Third  Edition,  by  Hamilton.  A  Complete  Text-book. 
By  C.  W.  Mansell  Moullin,  m.a.,  m.d.  (Oxon.),  f.r.c.s..  Surgeon  and  Lec- 
turer on  Physiology  to  the  London  Hospital ;  formerly  Radcliffe  Traveling 
Fellow  and  Fellow  of  Pembroke  College,  Oxford.  Third  American  Edition. 
Revised  and  edited  by  John  B.  Hamilton,  m.d.,  ll.d..  Professor  of  the  Principles 
of  Surgery  and  Clinical  Surgery,  Rush  Medical  College,  Chicago  ;  Professor  of 
Surgery,  Chicago  Polyclinic  ;  Surgeon,  formerly  Supervising  Surgeon-General, 
U.  S.  Marine  Hospital  Service ;  Surgeon  to  Presbyterian  Hospital ;  Consulting 
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Handsomely  bound  in  Cloth,  $6.00;  Leather,  $7.00;  Half  Russia,  $8.00 
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He  will  not  look  in  vain  for  details,  without  proper  attention  to  which  he  well  knows  that  the 
highest  success  is  impossible." — The  American  Journal  of  Medical  Sciences. 

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Enlargement  of  the   Prostate.     Its  Treatment   and   Radical   Cure.     Illus- 
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Inflammation  of  the  Bladder  and  Urinary  Fever.    Octavo.      Cloth,  $1.50 

MXJRRELL.     Massotherapeutics.     Massage  as  a  Mode  of  Treatment.     By  Wm. 
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minster Hospital.     Sixth  Edition.    Revised.    i2mo.  Preparing. 
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vised.    64mo.                                                                                          Cloth,  $1.00 

MUTER.  Practical  and  Analytical  Chemistry.  By  John  Muter,  f.r.s.,  f.c.s., 
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requirements  of  American  Medical  and  Pharmaceutical  Colleges.     56  Illus. 

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NAPHEYS'  Modern  Therapeutics.  Ninth  Revised  Edition,  Enlarged  and  Im- 
proved. In  Two  Handsome  Volumes.  Edited  by  Allen  J.  Smith,  m.d.,  Pro- 
fessor of  Pathology,  University  of  Texas,  Galveston,  late  Ass't  Demonstrator  of 
Morbid  Anatomy  and  Pathological  Histology,  Lecturer  on  Urinology,  University 
of  Pennsylvania;  and  J.  Aubrey  Davis,  m.d.,  Ass't  Demonstrator  of  Obstetrics, 
University  of  Pennsylvania;  Ass't  Physician  to  Home  for  Crippled  Children,  etc. 
Vol.  L— General  Medicine  and  Diseases  of  Children. 

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NEW  SYDENHAM  SOCIETY  Publications.  Three  to  Six  Volumes  published 
each  year.     List  of  Vohimes  up07i  application.  Per  annum,  $8.00 

NOTTER  and  FIRTH.  The  Theory  and  Practice  of  Hygiene.  A  Complete 
Treatise  by  J.  Lane  Notter,  m.a.,  m.d.,  f.c.s..  Fellow  and  Member  of  Council 
of  the  Sanitary  Institute  of  Great  Britain  ;  Professor  of  Hygiene,  Army  Medical 
School;  Examiner  in  Hygiene,  University  of  Cambridge,  etc.,  and  R.  H.  Firth, 
F.R.C.S.,  Assistant  Professor  of  Hygiene,  Army  Medical  School,  Netly.  Illustrated 
by  10  Lithographic  Plates  and  135  other  Illustrations,  and  including  many  Useful 
Tables.     Octavo.     1034  pages.  Cloth,  $7.00 

*^*This  volume  is  based  upon  Parkes'  Practical  Hygiene,  which  will  not  be  pub- 
lished hereafter. 


20  P.  BLAKISTON'S  SON  &*  CO.'S 

OETTEL.  Practical  Exercises  in  Electro-Chemistry.  By  Dr.  Felix  Oettel. 
Authorized  Translation  by  Edgar  F.  Smith,  m.a.,  Professor  of  Chemistry, 
University  of  Pennsylvania.     Illustrated.    '  Cloth,  .75 

Introduction  to  Electro-Chemical  Experiments.     Illustrated.     By  sanie 
Author  and  Translator.  Cloth,  .75 

OHLEMANN.  Ocular  Therapeutics  for  Physicians  and  Students.  By  M.  Ohle- 
MANX,  M.D.,  late  Physician  in  the  Ophthalmological  Clinical  Institute,  Royal 
Prussian  University  of  Berlin,  etc.  Translated  and  Edited  by  Charles  A. 
Oliver,  a.m.,  m.d.,  Attending  Surgeon  to  Wills  Eye  Hospital:  Ophthalmic 
Surgeon  to  the  Philadelphia  and  to  the  Presbyterian  Hospitals;  Fellow  of  the 
College  of  Physicians  of  Philadelphia,  etc.     i2mo.  Cloth,  $1.75 

ORMEROI).    Diseases  of  Nervous  System,  Student's  Guide  to.    By  J.  A.  Ormerod, 

M.D.  (Oxon.),  F.R.C.P.,  Physician  to  National  Hospital  for  Paralyzed  and  Epileptic 
and  to  City  of  London  Hospital  for  Diseases  of  the  Chest,  etc.  With  66  Wood 
Engravings.     i2mo.  Cloth,  $1.00 

OSGOOD.    The  "Winter  and  Its  Dangers.    By  HaxMIlton  Osgood,  m.d.  Cloth,  .40 

OSLER.    Cerebral  Palsies  of  Children.    A  Clinical  Study.    By  William  Osler, 

M.D.,  F.R.c.P.   (Lond.),  Professor  of  Medicine,  Johns    Hopkins  University,  etc. 

8vo.  Cloth,  $2.00 

Chorea  and  Choreiform  Affections.    8vo.  Cloth,  $2.00 

OSTROM.  Massage  and  the  Original  Swedish  Movements.  Their  Application 
to  Various  Diseases  of  the  Body.  A  Manual  for  Students,  Nurses  and  Physicians. 
By  KuRRE  W.  OsTROM,  from  the  Royal  University  of  Upsala,  Sweden;  Instructor 
in  Massage  and  Swedish  Movements  in  the  Hospital  of  the  University  of 
Pennsylvania,  and  in  the  Philadelphia  Polyclinic  and  College  for  Graduates  in 
Medicine,  etc.  Fourth  Edition,  Enlarged.  With  105  Illustrations,  many  of 
which  were  drawn  especially  for  this  purpose.    i2mo.  Cloth,  gi.oo 

PACKARD'S  Sea  Air  and  Sea  Bathing.    By  John  H.  Packard,  m.d.     Cloth,  .40 

PARKES'  Practical  Hygiene.  By  Edward  A.  Parkes,  m.d.  Superseded  by 
"  Notter  and  Firth  "  Treatise  on  Hygiene.     See  previous  page. 

PARKES.  Hygiene  and  Public  Health.  A  Practical  Manual.  By  Louis  C. 
Parkes,  m.d.,  d.p.h.  Lond.  Univ.,  Lect.  on  Public  Health  at  St.  George's  Hos- 
pital, Medical  Officer  of  Health,  Parish  of  Chelsea,  London,  etc.  Fifth  Edition, 
Enlarged  and  Revised.     80  Illustrations.     i2mo.  Cloth,  $2.50 

The    Elements    of    Health.      An    Introduction   to  the  Study   of   Hygiene. 
Illustrated.  Cloth,  $1.25 

PARRISH'S  Alcoholic  Inebriety.  From  a  Medical  Standpoint,  with  Illustrative 
Cases  from  the  Clinical  Records  of  the  Author.  By  Joseph  Parrish,  m.d., 
President  of  the  Amer.  Assoc,  for  Cure  of  Inebriates.  Cloth,  $1.00 

PHILLIPS.  Spectacles  and  Eyeglasses,  Their  Prescription  and  Adjustment.  By 
R.  J.  Phillips,  m.d..  Instructor  on  Diseases  of  the  Eye,  Philadelphia  Polyclinic, 
Ophthalmic  Surgeon,  Presbyterian  Hospital.  Second  Edition,  Revised  and 
Enlarged.     49  Illustrations.     i2mo.  Cloth,  $1.00 

"  This  liule  work  now  appears  in  the  form  of  a  revised  second  edition  of  lOl  pages.  It 
is  of  convenient  size  and  is  excellently  printed.  The  book  is  issued  as  an  aid  to  those  who  pre- 
scribe and  who  sell  eyeglasses  and  spectacles,  for  the  purpose  of  enaljling  them  to  reach  the  most 
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proper  arljustment  of  spectacles  and  eyeglasses  is  of  very  great  importance,  it  is  desirable  that 
the  rules  and  suggestions  contained  in  this  little  volume  should  be  familiar  to  every  oculist  and 
optician." — The  Medical  Record,  A^ew  York. 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  21 

PHYSICIAN'S  VISITING  LIST.    Published  Annually.    Forty-eighth  Year  (1899) 
of  its  Publication. 

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50  2  vols.     I  July  to  Dec.  I 

,,  ,,  1         (  fan.  to  Tune  I   ,,  ,,  ,,         ,,         ,, 

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POTTER.  A  Handbook  of  Materia  Medica,  Pharmacy,  and  Therapeutics,  in- 
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Practical  Pharmacy,  and  Minute  Directions  for  Prescription  Writing,  etc.  In- 
cluding over  600  Prescriptions  and  Formulae.  By  Samuel  O.  L.  Potter,  m.a., 
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Clinical  Medicine  in  the  College  of  Physicians  and  Surgeons,  San  Francisco ; 
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Compend  of  Anatomy,  including  Visceral  Anatomy.  Sixth  Edition.  Re- 
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Speech  and  Its  Defects.  Considered  Physiologically,  Pathologically  and 
Remedially;  being  the  Lea  Prize  Thesis  of  Jefferson  Medical  College,  1882. 
Revised  and  Corrected.     i2mo.  Cloth,  gi.oo 

POWELL.    Diseases  of  the  Lungs  and  Pleurae,  Including  Consumption.    By 

R.  Douglas  Powell,  m.d.,  f.r.c.p.,  Physician  to  the  Middlesex  Hospital,  and 
Consulting  Physician  to  the  Hospital  for  Consumption  and  Diseases  of  the  Chest 
at  Brompton,  Fourth  Edition.  With  Colored  Plates  and  Wood  Engravings. 
8vo.  Cloth,  $4.00 

POWER.  Surgical  Diseases  of  Children  and  their  Treatment  by  Modern 
Methods.  By  D'Arcy  Power,  m.a.,  f.r.c.s.  (Eng.),  Demonstrator  of  Operative 
Surgery,  St.  Bartholomew's  Hospital ;  Surgeon  to  the  Victoria  Hospital  for 
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22  P.  BLAKISTON'S  SON  &-  CO.'S 

PRESTON.  Hysteria  and  Certain  Allied  Conditions.  Their  Nature  and  Treat- 
ment. With  special  reference  to  the  appHcation  of  the  Rest  Cure,  Massage, 
Electro-therapy,  Hypnotism,  etc.  By  George  J.  Preston,  m.d..  Professor  of 
Diseases  of  the  Nervous  System,  College  of  Physicians  and  Surgeons,  Balti- 
more ;  Visiting  Physician  to  the  City  Hospital ;  Consulting  Neurologist  to  Bay 
View  Asylum  and  the  Hebrew  Hospital ;  Member  American  Neurological  Asso- 
ciation, etc.     With  Illustrations.     i2mo.  Cloth,  $2.00 

PRITCHARD.  Handbook  of  Diseases  of  the  Ear.  By  Urban  Pritchard, 
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geon to  King's  College  Hospital,  Senior  Surgeon  to  the  Royal  Ear  Hospital,  etc. 
Third  Edition,  Enlarged.    Many  Illustrations  and  Formulas.    i2mo.    Cloth,  $1.50 

PROCTOR'S  Practical  Pharmacy.  Lectures  on  Practical  Pharmacy.  With  Wood 
Engravings  and  32  Lithographic  Fac -simile  Prescriptions.  By  Barnard  S. 
Proctor.  Third  Edition.  Revised  and  with  elaborate  Tables  of  Chemical 
Solubilities,  etc.  Cloth,  $3.00 

REESE'S  Medical  Jurisprudence  and  Toxicology.  A  Text-book  for  Medical  and 
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Jurisprudence,  Professor  of  the  Principles  and  Practice  of  Medical  Jurisprudence, 
including  Toxicology,  in  the  University  of  Pennsylvania  Medical  Department. 
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Professor  of  Chemistry,  Woman's  Medical  College  of  Penna.,  etc.  i2mo.  645 
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"  To  the  student  of  medical  jurisprudence  and  toxicology  it  is  invaluable,  as  it  is  concise, 

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REEVES.  Medical  Microscopy.  Illustrated.  A  Handbook  for  Physicians  and 
Students,  including  Chapters  on  Bacteriology,  Neoplasms,  Urinary  Examination, 
etc.  By  James  E.  Reeves,  m.d.,  Ex-President  American  Public  Health  Associa- 
tion, Member  Association  American  Physicians,  etc.  Numerous  Illustrations, 
some  of  which  are  printed  in  colors.  i2mo.     Handsome  Cloth,  |2. 50 

REGIS.  Mental  Medicine.  A  Practical  Manual.  By  Dr.  E.  R6gis,  formerly 
Chief  of  Clinique  of  Mental  Diseases,  Faculty  of  Medicine  of  Paris  ;  Physician 
of  the  Maison  de  Sante  de  Castel  d'Andorte  ;  Professor  of  Mental  Diseases, 
Faculty  of  Medicine,  Bordeaux,  etc.  With  a  Preface  by  M.  Benjamin  Ball, 
Clinical  Professor  of  Mental  Diseases,  Faculty  of  Medicine,  Paris.  Authorized, 
Translation  from  the  Second  Edition  by  H.  M.  Bannister,  m.d.,  late  Senior 
Assistant  Physician,  Illinois  Eastern  Hospital  for  the  Insane,  etc.  With  an  In- 
troduction by  the  Author.     i2mo.     692  pages.  Cloth,  $2.00 

RICHARDSON.  Long  Life,  and  How  to  Reach  It.  By  J.  G.  Richardson,  Prof, 
of  Hygiene,  University  of  Pennsylvania.  Cloth,  .40 

RICHARDSON'S  Mechanical  Dentistry.  A  Practical  Treatise  on  Mechanical 
Dentistry.  By  Joseph  Richardson,  d.d.s.  Seventh  Edition.  Thoroughly 
Revised  and  in  many  parts  Rewritten  by  Dr.  Geo.  W.  Warren,  Chief  of  the 
Clinical  Staff,  Pennsylvania  College  of  Dental  Surgery,  Philadelphia.  With  691 
Illustrations,  many  of  which  are  from  original  Wood  Engravings.  Octavo, 
675  pages.  Cloth,  $5.00;  Leather,  $6.00 ;  Half  Russia,  $7.00 

ROBERTS.  Practice  of  Medicine.  The  Theory  and  Practice  of  Medicine.  By 
Frederick  Roberts,  m.d..  Professor  of  Therapeutics  at  University  College, 
London.    Ninth  Edition,  with  Illustrations.    8vo.        Cloth,  ^4.50;  Leather,  )?5. 50 

ROBERTS.  Fractures  of  the  Radius.  A  Clinical,  Pathological,  and  Experimental 
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Philadelphia  Polyclinic,  etc.     33  Illustrations.     8vo.  Cloth,  $i.co 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  23 

RICHTER'S  Inorganic  Chemistry.    A  Text-book  for  Students.    By  Prof.  Victor 

VON   RiCHTER,    University  of  Breslau.     Fourth  American,  from  Sixth  German 

Edition.      Authorized   Translation   by  Edgar  F.  Smith,  m.a.,  ph.d.,  Prof,  of 

Chemistry,  University  of  Pennsylvania,  Member  of  the  Chemical  Societies  of 

Berlin  and  Paris.    89  Illustrations  and  a  Colored  Plate.     i2mo.  Cloth,  $1.75 

Organic  Chemistry.      The  Chemistry  of  the   Carbon    Compounds.      Third 

American  Edition,  translated  from  the  Eighth  German  by  Edgar  F.  Smith, 

M.A.,  PH.D.,  Professor  of  Chemistry,  University  of  Pennsylvania.  Revised  and 

Enlarged.     Illus.     2  vols.     i2mo.     Vol.    I.     Aliphadc  Series.     625  pages. 

Cloth,  $3.00 
Vol.  II.     Carbocyclic  Series.       Nearly  Heady. 

ROBINSON.  Latin  Grammar  of  Pharmacy  and  Medicine.  By  p.  H.  Robinson, 
PH.D.,  Professor  of  Latin  Language  and  Literature,  University  of  Kansas.  Intro- 
duction by  L.  E.  Sayre,  ph.g.,  Professor  of  Pharmacy  in,  and  Dean  of  the  Dept. 
of  Pharmacy,  University  of  Kansas.  Third  Edition.  Revised  with  the  help 
of  Prof.  L.  E.  Sayre,  of  University  of  Kansas,  and  Dr.  Charles  Rice,  of  the 
College  of  Pharmacy  of  the  City  of  New  York.     i2mo.  Cloth,  $1.75 

ST.  CLAIR.  Medical  Latin.  Designed  expressly  for  the  Elementary  Training 
of  Medical  Students.  By  W,  T.  St.  Clair,  Instructor  in  Latin  in  the  Kentucky 
School  of  Medicine  and  in  the  Louisville  Male  High  School.    i2mo.    Cloth,  $1.00 

SANSOM.  Diseases  of  The  Heart.  The  Diagnosis  and  Pathology  of  Diseases  of 
the  Heart  and  Thoracic  Aorta.  By  A.  Ernest  Sansom,  m.d.,  f.r.c.p..  Physician 
to  the  London  Hospital,  etc.     With  Illustrations.     8vo.  Cloth,  $6.00 

SAYRE.  Organic  Materia  Medica  and  Pharmacognosy.  An  Introduction 
to  the  Study  of  the  Vegetable  Kingdom  and  the  Vegetable  and  Animal  Dnjgs. 
Comprising  the  Botanical  and  Physical  Characteristics,  Source,  Constituents. 
Pharmacopoeial  Preparations.  Insects  Injurious  to  Drugs,  and  Pharmacal 
Botany.  By  L.  E.  Sayre,  b.s.,  ph.m.,  Dean  of  the  School  of  Pharmacy  ; 
Professor  of  Materia  Medica  and  Pharmacy  in  the  University  of  Kansas  ;  Mem- 
ber Committee  of  Revision  of  the  United  States  Pharmacopoeia,  etc.  With 
Sections  on  Histology  and  Microtechnique,  by  William  C.  Stevens,  Professor 
of  Botany  in  the  University  of  Kansas.  Second  Edition,  Revised  and  En- 
larged, with  374  Illustrations,  the  majority  of  which  are  from  original  drawings. 
8vo.    Just  Ready.  .  Cloth,  $4.50 

SCHAMBERGr.  Compend  of  Diseases  of  the  Skin.  By  Jay  F.  Schamberg, 
Associate  in  Skin  Diseases,  Philadelphia  Polychnic  ;  Quiz-Master  at  University 
of  Pennsylvania.     99  Illustrations.  Cloth,  .80.     Interleaved,  $1.25 

SCHREINER.  Diet  List.  Arranged  in  the  Form  of  a  Chart  on  which  Articles  of 
Diet  can  be  indicated  for  any  Disease.  By  E.  R.  Schreiner,  m.d.,  Ass't  Dem. 
of  Physiology,  University  of  Penna.  Put  up  in  Pads  of  50  with  Pamphlet  of 
Specimen  Dietaries.  Per  Pad,    .75 

SCOVILLE.  The  Art  of  Compounding.  A  Text-book  for  Students  and  a  Refer- 
ence Book  for  Pharmacists.  By  Wilbur  L.  Scoville,  ph.g.,  Professor  of  Ap- 
phed  Pharmacy  and  Director  of  the  Pharmaceutical  Laboratory  in  the  Massa- 
chusetts College  of  Pharmacy.     Second  Edition,  Enlarged  and  Improved. 

Cloth,  $2.50;  Sheep,  $3.50;  Half  Russia,  $4.50 

SEWELL.  Dental  Surgery,  including  Special  Anatomy  and  Surgery.  By  Henry 
Sewell,  M.R.C.S.,  L.D.S.,  President  Odontological  Society  of  Great  Britain.  3d 
Edition,  greatly  enlarged,  with  about  200  Illustrations.  Cloth,  $2.00 

SHAWE.  Notes  for  Visiting  Nurses,  and  all  those  interested  in  the  working  and 
organization  of  District,  Visidng,  or  Parochial  Nurse  Societies.  By  Rosalind 
Gillette  Shawe,  District  Nurse  for  the  Brooklyn  Red  Cross  Society.  With  an 
Appendix  explaining  the  organization  and  working  of  various  Visiting  and  Dis- 
trict Nurse  Societies,  by  Helen  C.  Jenks,  of  Philadelphia.     i2mo.    Cloth,  ^i.oo 


24  P.  BLAKISTON'S  SON  <&-  CO:S 

SMITH.  Abdominal  Surgery.  Being  a  Systematic  Description  of  all  the  Princi- 
pal Operations.  By  J.  Greig  Smith,  m.a.,  f.r.s.e.,  Surg,  to  British  Royal  In- 
firmary. 224  Illustrations.  Sixth  Edition.  Enlarged  and  Thoroughly  Revised 
by  James  Swain,  m.d.  (Lond.),  f.r.c.s..  Professor  of  Surgery,  University  College, 
Bristol,  etc.     2  Volumes.     Octavo.  Cloth,  Sio.oo 

SMITH.  Electro-Chemical  Analysis.  By  Edgar  F.  Smith,  Professor  of  Chem- 
istry, University  of  Pennsylvania.  Second  Edition,  Revised  and  Enlarged.  27 
Illustrations.     i2mo.  Cloth,  $1.25 

*^*  See  also  Oettel  and  Richter. 

SMITH  and  KELLER.  Experiments.  Arranged  for  Students  in  General  Chem- 
istry. By  Edgar  F.  Smith,  Professor  of  Chemistry,  University  of  Pennsylvania, 
and  Dr.  H.  F.  Keller,  Professor  of  Chemistry,  Philadelphia  High  School.  Third 
Edition.     8to.     Illustrated.  Cloth,  .60 

SMITH.  Dental  Metallurgy.  A  Manual.  By  Ernest  A.  Smith,  f.c.s.,  Asst. 
Instructor  in  Metallurgy  Royal  College  of  Science,  London.     Illustrated.     i2mo. 

Cloth,  $1.75 

SMITH.  Wasting'  Diseases  of  Infants  and  Children.  By  Eustace  Smith,  m.d., 
F.R.C.P.,  Physician  to  the  East  London  Hospital  for  Children,  etc.  Sixth  Edition, 
Revised.  Cloth,  §2.00 

STAMMER.  Chemical  Problems,  with  Explanations  and  Answers.  By  Karl 
Stammer.  Translated  from  the  Second  German  Edition,  by  Prof.  W.  S.  Hos- 
KINSOK,  a.m.,  Wittenberg  College,  Springfield,  Ohio.     i2mo.  Cloth.  .50 

STARLING.  Elements  of  Human  Physiology.  By  Ernest  H.  Starling,  m.d. 
Lond.,  m.r.c.p.,  Joint  Lecturer  on  Physiology  at  Guy's  Hospital,  London, 
etc.     With  100  Illustrations.      i2mo.     437  pages.  Cloth,  Si.oo 

STARR.  The  Digestive  Organs  in  Childhood.  Second  Edition.  The  Diseases 
of  the  Digestive  Organs  in  Infancy  and  Childhood.  With  Chapters  on  the 
Investigation  of  Disease  and  the  Management  of  Children.  By  Louis  Starr, 
M.D.,  late  Clinical  Prof,  of  Diseases  of  Children  in  the  Hospital  of  the  University 
of  Penn'a;  Physician  to  the  Children's  Hospital,  Phila.  Second  Edition. 
Revised  and  Enlarged.  Illustrated  by  two  Colored  Lithograph  Plates  and 
numerous  Wood  Engravings.     Crown  Octavo.  Cloth,  $2.00 

The  Hygiene  of  the  Nursery,  including  the  General  Regimen  and  Feed- 
ing of  Infants  and  Children,  and  the  Domestic  Management  of  the  Ordinary 
Emergencies  of  Early  Life,  Massage,  etc.  Sixth  Edition.  Enlarged.  25 
Illustrations.     i2mo.     280  pages.  Cloth,  $1.00 

STEARNS.  Lectures  on  Mental  Diseases.  By  Henry  Putnam  Stearns,  m.d., 
Physician  Superintendent  at  the  Hartford  Retreat,  Lecturer  on  Mental  Diseases 
in  Yale  University,  Member  of  the  American  Medico-Psychological  Ass'n,  Hon- 
orar\^  Member  of  the  British  Medico-Pyschological  Society.  With  a  Digest  of 
Laws  of  the  Various  States  Relating  to  Care  of  Insane.    Illustrated. 

Cloth,  $2.75  ;  Sheep,  S3.25 

STEVENSON  and  MURPHY.    A  Treatise  on  Hygiene.    By  Various  Authors. 
Edited  by  Thomas  Stevenson,  m.d.,  f.r.c.p..  Lecturer  on  Chemistry  and  Medi- 
cal Jurisprudence  at  Guy's    Hospital,  London,  etc.,  and  Shirley  F.  Murphy, 
Medical  Officer  of  Health  to  the  County  of  London.    In  Three  Octavo  Volumes. 
Vol.  I.    With  Plates  and  Wood  Engravings.    Octavo.  Cloth,  $6.00 

Vol.  II.     With  Plates  and  Wood  Engravings.     Octavo.  Cloth,  g6.oo 

Vol.  III.     Sanitary  Law.     Octavo.  Cloth,  $5.00 

* ^  Special  Circular  upon  applicatioti. 

STEWART'S  Compend  of  Pharmacy.  Based  upon  "  Remington's  Text-Book  of 
Pharmacy."  By  F.  E.  Stewart,  m.d.,  ph. g., Quiz-Master  in  Chem.  and  Theoreti- 
cal Pharmacy,  Phila.  College  of  Pharmacy;  Lect.  in  Pharmacology,  Jefferson 
Medical  College.  Fifth  Ed.  Revised  in  accordance  with  U.  S.  P.,  1890.  Com- 
plete tables  of  Metric  and  English  Weights  and  Measures.  ? Quiz- Compend f 
Series.  Cloth,  .80;  Interleaved  for  the  addition  of  notes,  $1.25 


MEDICAL  AND  SCIENTIFIC  PUBLIC  A  TIONS.  25 

STIRLING.  Outlines  of  Practical  Physiology.  Including  Chemical  and  Experi- 
mental Physiology,  with  Special  Reference  to  Practical  Medicine.  By  W.  Stir- 
ling, M.D.,  Sc.D.,  Professor  of  Physiology  and  Histology,  Owens  College,  Victoria 
University,  Manchester.  Exami'ner  in  Physiology,  Universities  of  Edinburgh 
and  London.     Third  Edition.     289  Illustrations.  Cloth,  $2.00 

STIRLING.  Outlines  of  Practical  Histology.  368  Illustrations.  Second  Edi- 
tion.    Revised  and  Enlarged',  with  new  Illustrations.     i2mo.  Cloth,  $2.00 

STOHR.     Text-Book  of  Histology,  Including   the  Microscopical    Technic. 

By  Dr.  Philipp  Stohr,  Professor  of  Anatomy  at  University  of  Wiirzburg. 
Authorized  Translation  by  Emma  L.  Billstein,  m.d.,  Demonstrator  of  Histology 
and  Embryology,  Woman's  Medical  College  of  Pennsylvania.  Edited,  with 
Additions,  by  Dr.  Alfred  Schaper,  Demonstrator  of  Histology  and  Embry- 
ology, Harvard  Medical  School,  Boston.  Second  American  from  the  Eighth 
German  Edition,  Enlarged  and  Revised.    292  Illustrations.    Octavo.    Cloth,  $3.00 

STRAHAN.  Extra-Uterine  Pregnancy.  The  Diagnosis  and  Treatment  of  Extra- 
Uterine  Pregnancy.  Being  the  Jenks  Prize  Essay  of  the  College  of  Physicians 
of  Philadelphia.  By  John  Strahan,  m.d.  (Univ.  of  Ireland),  late  Res.  Surgeon 
Belfast  Union  Infirmary  and  Fever  Hospital.     Octavo.  Cloth,  .75 

SUTTON'S  Volumetric  Analysis.  A  Systematic  Handbook  for  the  Quantitative 
Estimation  of  Chemical  Substances  by  Measure,  Applied  to  Liquids,  Solids  and 
Gases.  Adapted  to  the  Requirements  of  Pure  Chemical  Research,  Pathological 
Chemistry,  Pharmacy,  Metallurgy,  Photography,  etc.,  and  for  the  Valuation  of 
Substarices  Used  in  Commerce,  Agriculture,  and  the  Arts.  By  Francis  Sutton, 
F.c.S.     Seventh  Edition,  Revised  and  Enlarged,  with  112  Illustrations.     8vo. 

Cloth,  $4.50 

SWAIN.  Surgical  Emergencies,  together  with  the  Emergencies  Attendant  on 
Parturition  and  the  Treatment  of  Poisoning.  A  Manual  for  the  Use  of  Student, 
Practitioner,  and  Head  Nurse.  By  William  Paul  Swain,  f.r.c.s..  Surgeon  to 
the  South  Devon  and  East  Cornwall  Hospital,  England.  Fifth  Edition.  i2mo. 
149  Illustrations.  Cloth,  $1.75 

SWANZY.    Diseases  of  the  Eye  and  their  Treatment,    A  Handbook  for  Physi- 
cians and  Students.     By  Henry  R.  Swanzy,  a.m.,  m.b.,  f.r.c.s. i.,  Surgeon  to 
the  National  Eye  and  Ear  Infirmary  ;  Ophthalmic  Surgeon  to  the  Adelaide  Hos- 
pital, Dublin.     Sixth    Edition,  Thoroughly  Revised  and  Enlarged.     158  Illus- 
trations, one  Plain  Plate,  and  a  Zephyr  Test  Card.     i2mo.  Cloth,  $3.00 
"  Is  without  doubt  the  most  satisfactory  manual  we  have  upon  diseases  of  the  eye.     It  occu- 
pies the  middle  ground  between  the  students'  manuals,  which  are  too  brief  and  concise,  and  the 
encyclopedic  treatises,  which  are  too  extended  and  detailed  to  be  of  special  use  to  the  general 
practitioner." — Chicago  Medical  Recorder. 

SYMONLS.  Manual  of  Chemistry,  for  Medical  Students.  By  Brandreth 
Symonds,  a.m.,  m.d.,  Ass't  Physician  Roosevelt  Hospital,  Out-Patient  Department ; 
Attending  Physician  Northwestern  Dispensary,  New  York.  Second  Edition. 
l2mo.  Cloth,  $2.00 

TAFT.  Index  of  Dental  Periodical  Literature.  By  Jonathan  Taft,  d.d.s. 
Svo.  Cloth,  ;g2.oo 

TALBOT.  Irregularities  of  the  Teeth,  and  Their  Treatment.  By  Eugene  S. 
Talbot,  m.d..  Professor  of  Dental  Surgery  Woman's  Medical  College,  and 
Lecturer  on  Dental  Pathology  in  Rush  Medical  College,  Chicago.  Second  Edi- 
tion, Revised.     Octavo.      234  Illustrations.     261  pages.  Cloth,  $3.00 

TANNER'S  Memoranda  of  Poisons  and  their  Antidotes  and  Tests.  By  Thos. 
Hawkes  Tanner,  m.d.,  f.r.c.p.  7th  American,  from  the  Last  London  Edition. 
Revised  by  John  J.  Reese,  m.d..  Professor  Medical  Jurisprudence  and  Toxi- 
cology in  the  University  of  Pennsylvania.     i2mo.  Cloth,  .75 

TAYLOR.  Practice  of  Medicine.  A  Manual.  By  Frederick  Taylor,  m.d.. 
Physician  to,  and  Lecturer  on  Medicine  at,  Guy's  Hospital,  London  ;  Physician  to 
Evelina  Hospital  for  Sick  Children,  and  Examiner  in  Materia  Medica  and  Phar- 
maceutical Chemistry,  University  of  London.     Fifth  Edition.  Cloth,  I4.00 


26  P.  BLAKISTON'S  SON  &-  CO.'S 

TAYLOR  AND  WELLS.  Diseases  of  Children.  A  Manual  for  Students  and 
Physicians.  By  John  Madison  Taylor,  a.b.,  m.d.,  Professor  of  Diseases  of 
Children,  Philadelphia  Polyclinic ;  Assistant  Physician  to  the  Children's  Hospi- 
tal and  to  the  Orthopedic  Hospital ;  Consulting  Physician  to  the  Elwyn  and  the 
Vineland  Training  Schools  for  Feeble-Minded  Children ;  Neurologist  to  the 
Howard  Hospital,  etc. ;  and  William  H.  Wells,  m.d.,  Adjunct-Professor  of 
Obstetrics  and  Diseases  of  Infancy  in  the  Philadelphia  Polyclinic  ;  late  Assistant 
Demonstrator  of  Clinical  Obstetrics  and  Diseases  of  Infancy  in  Jefferson  Medi- 
cal College.    With  8  Plates  and  numerous  other  Illustrations.    i2mo.    743  pages. 

Cloth,  ^4.00 

TEMPERATURE  Charts  for  Recording  Temperature,  Respiration,  Pulse,  Day  of 
Disease,  Date,  Age,  Sex,  Occupation,  Name,  etc.  Put  up  in  pads;  each  .50 

THOMPSON.  TTrinary  Organs.  Diseases  of  the  Urinary  Organs.  Containing  32 
Lectures.  By  Sir  Henry  Thompson,  f.r.c.s..  Emeritus  Professor  of  Clinical  Sur- 
gery in  University  College.  Eighth  London  Edition.  121  Illustrations.  Octavo. 
470  pages.  Cloth,  ^3.00 

THORINGTON.  Retinoscopy  (The  Shadow  Test)  in  the  Determination  of 
Refraction  at  One  Metre  Distance  with  the  Plane  Mirror.  By  James  Thoring- 
TON,  A.M.,  M.D.,  Adjunct  Professor  of  Diseases  of  the  Eye  in  the  Philadelphia  Poly- 
clinic ;  Assistant  Surgeon  Wills  Eye  Hospital ;  Associate  Member  American 
Ophthalmological  Society;  Ophthalmologist  to  the  Elwyn  and  Vineland  Train- 
ing Schools ;  Lecturer  on  the  Anatomy,  Physiology,  and  Care  of  the  Eyes  in 
the  Philadelphia  Manual  Training  Schools,  etc.  With  38  Illustrations,  several 
of  which  are  Colored.     Third  Edition,  Enlarged.     i2mo.  Cloth,  $1.00 

Refraction  and  How  to  Refract.  With  200  Illustrations,  most  of  which 
are  made  from  original  Drawings,  and  thirteen  of  which  are  in  colors. 
i2mo.     300  pages.  Cloth,  $1.50 

Synopsis  of  Contents. — I.  Optics.  11.  The  Eye;  The  Standard  Eye; 
Cardinal  Points;  Visual  Angle  ;  Minimum  Visual  Angle ;  Standard  Acuteness  of 
Vision  ;  Size  of  Retinal  Image  Accommodation  ;  Mechanism  of  Accommodation  ; 
Far  and  Near  Point ;  Determ.ination  of  Distant  Vision  and  Near  Point ;  Ampli- 
tude of  Accommodation;  Convergence;  Angle  Gamma;  Angle  Alpha.  III. 
Ophthalmoscope;  Direct  and  Indirect  Method.  IV.  Emmetropia  ;  Hyperopia; 
Myopia.  V.  Astigmatism  or  Curvature  Ametropia  ;  Tests  for  Astigmatism.  VI. 
Retinoscopy.  VII.  Muscles.  VIII.  Cycloplegics ;  Cycloplegia ;  Asthenopia; 
Examination  of  the  Eyes.  IX.  How  to  Refract.  X.  Applied  Refraction.  XI. 
Presbyopia;  Aphakia;  Anisometropia;  Spectacles.  XII.  Lenses;  Spectacle 
and  Eye  Glass  Frames;  How  to  Take  Measurements  for  Them  and  How  They 
Should  be  Fitted. 

THORNE.  The  Schott  Methods  of  the  Treatment  of  Chronic  Diseases  of  the 
Heart.  With  an  Account  of  the  Nauheim  Baths  and  of  the  Therapeutic  Exer- 
cises. By  W.  Bezly  Thorne,  m.d.,  m.r.c.p.  With  Plates  and  Numerous 
Other  Illustrations.    Third  Edition,  Revised  and  Enlarged.    Octavo.    Cloth,  $1.75 

TOMES'  Dental  Anatomy,    A  Manual  of  Dental  Anatomy,  Human  and  Compara- 
tive.    By  C.  S.  Tomes,  d.d.s.     263  Illustrations.     5th  Ed.     i2mo.     Cloth,  $4.00 
Dental  Surgery.     A  System  of   Dental  Surgery.    By  John  Tomes,  f.r.s. 
Fourth  Edition,  Thoroughly  Revised.      By  C.  S.  Tomes,  d.d.S.     With  289 
Illustrations.     i2mo.     717  pages.  Cloth,  $4.00 

TREVES.  German-English  Medical  Dictionary.    By  Frederick  Treves,  f.r.c.s., 

assisted  by  Dr.  Hugo  Lang,  b.a.  (Munich).     i2mo.  }4  Russia,  $3.25 

Physical  Education,  Its  Effects,  Value,  Methods,  etc.  Cloth,  .75 

TTJKE.  Dictionary  of  Psychological  Medicine.  Giving  the  Definition,  Ety- 
mology, and  Synonyms  of  the  Terms  used  m  Medical  Psychology,  with  the 
Symptoms,  Pathology,  and  Treatment  of  the  recognized  forms  of  Mental  Dis- 
orders, together  with  the  Law  of  Lunacy  in  Great  Britain  and  Ireland.  Edited  by 
D.  Hack  Tuke,  m.d.,ll.d.,  Examiner  in  Mental  Physiology  in  the  University 
of  London.     Two  Volumes.     Octavo.     1477  pages.  Cloth,  $10.00 


MEDICAL  AND  SCIENTIFIC  PUBLICA  TIONS.  27. 

TRAUBE.  Physico-Chemical  Methods.  By  Dr.  J.  Traube,  Privatdocent  in 
the  Technical  High  School  of  Berlin.  Authorized  Translation  by  W.  D.  Har- 
din, Harrison  Senior  Fellow  in  Chemistry,  University  of  Pennsylvania.  With 
97  Illustrations.     8vo.  Cloth,  $1.50 

THRESH.  Water  and  "Water  Supplies.  By  John  C.  Thresh,  d.s.c.  (London), 
M.D.,  D.P.H.  (Cambridge),  Medical  Officer  of  Health  to  the  Essex  County 
Council;  Lecturer  on  Public  Health,  King's  College,  London ;  Fellow  of  the 
Institute  of  Chemistry  ;  Member  Society  Public  Analysts,  etc.  Second  Edition. 
Revised.     Illustrated.     i2mo.     438  pages.    Just  Ready.  Cloth,  $2.00 

TURNBTTLL'S  Artificial  Anaesthesia.  A  Manual  of  Anesthetic  Agents  in  the 
Treatment  of  Diseases  also  their  Employment  in  Dental  Surgery  ;  Modes  of  Ad- 
ministration ;  Considering  their  Relative  Risks ;  Tests  of  Purity ;  Treatment  of 
Asphyxia;  Spasms  of  the  Glottis;  Syncope,  etc.  By  Laurence  Turnbull,  m.d., 
PH.G.,  Aural  Surgeon  to  Jefferson  College  Hospital,  etc.  Fourth  Edition,  Re- 
vised and  Enlarged.     54  Illustrations.     i2mo.  Cloth,  $2.50 

TTTSON.  Veterinary  Pharmacopoeia,  including  the  outlines  of  Materia  Medica 
and  Therapeutics.  By  Richard  V.  TusoN,  late  Professor  at  the  Royal  Veter- 
inary College.  Fifth  Edition.  Revised  and  Edited  by  James  Bayne,  f.c.s., 
Professor  of  Chemistry  and  Toxicology  at  the  Royal  Veterinary  College.     i2mo. 

Cloth,  $2.25 

TTTSSEY.  High  Altitude  Treatment  for  Consumption.  The  Principles  or 
Guides  for  a  Better  Selection  or  Classification  of  Consumptives  Amenable  to 
High  Altitude  Treatment,  and  to  the  Selection  of  Patients  who  may  be  More 
Successfully  Treated  in  the  Environment  to  which  They  were  Accustomed 
Previous  to  Their  Illness.  By  A.  Edgar  Tussey,  m.d.,  Adjunct  Professor  of 
Diseases  of  the  Chest  in  the  Philadelphia  Polyclinic  and  School  for  Graduates 
in  Medicine,  etc.     i2mo.  Cloth,  $1.50 

TYSON.     The  Practice  of  Medicine.     A  Text-Book  for  Physicians  and  Students, 
with  Special  Reference  to  Diagnosis  and  Treatment.     By  James  Tyson,  m.d.. 
Professor  of  Chnical  Medicine  in  the  University  of  Pennsylvania,  Physician  to 
the  University  and  to  the  Philadelphia  Hospitals,  etc.     With  Colored  Plates  and 
many  other  Illustrations.   Svo.    Cloth,  ^5.50;  Leather,  $6.50;  Half  Russia,  $7.50 
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he  has  been  associated  with  the  University  of  Pennsylvania   and  the  Philadelphia   Hospital  for 
nearly  thirty  years.     Moreover,  he  entered  medicine  through  the  portal  of  pathology,  a  decided 
advantage  in  the  writer  of  a  text-book.      .      .     .     The  typography  is  decidedly  above  works  of 
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*^*  Sample  Pages  and  Illustrations  Sent  Free  upon  Application. 

Guide  to  the  Examination  of  Urine.     Ninth  Edition.     For  the  Use  of 

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Engraved  on  Wood.  Ninth  Edition.  Revised.   i2mo.  276  pages.    Cloth,  ^1.25 
*4{.*  A  French  translation  of  this  book  has  recently  appeared  in  Paris. 

Handbook  of  Physical  Diagnosis.  3d  Edition.  Revised  and  Enlarged. 
With  Colored  and  other  Illustrations.     i2mo.     278  pages.  Cloth,  $1.50 

Cell  Doctrine.    Its  History  and  Present  State.     Second  Edition.     Cloth,  $1.50 

UNITED  STATES  PHARMACOP(EIA.  1890.  Seventh  Decennial  Revision. 
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28  P.  BLAKISTON'S  SON  6-  CO:S 


ULZEE,  and   FRAENKEL.     Introduction  to  Chemical-Technical  Analysis. 

By  Prof.  F.  Ulzer  and  Dr.  A.  Fraexkel,  Directors  of  the  Testing  Laboratory 
ot  the  Royal  Technological  Museum,  Vienna.  Authorized  Translation  by 
Hermann  Fleck,  Nat.  Sc.D.,  Instructor  in  Chemistry  and  Chemical  Technical 
Analysis  in  the  John  Harrison  Laboratory  of  Chemistry,  University  of  Pennsyl- 
vania, with  an  Appendix  by  the  Translator  relating  to  Food  Stuffs,  Asphaltum 
and  Paint.     12  Illustrations.     8vo.  Cloth,  $1.25 

VAN  NtJYS  on  The  Urine.  Chemical  Analysis  of  Healthy  and  Diseased  Urine, 
Qualitative  and  Quantitative.  By  T.  C.  Van  Nuys,  Professor  of  Chemistry 
Indiana  University.     39  Illustrations.     Octavo.  Cloth,  ^i.cx) 

VAN  HARLINGEN  on  Skin  Diseases.  A  Practical  Manual  of  Diagnosis  and 
Treatment  with  special  reference  to  Differential  Diagnosis.  By  Arthur  Van 
Harlingen,  M.D.,  Professor  of  Diseases  of  the  Skin  in  the  Philadelphia  Poly- 
clinic ;  CUnical  Lecturer  on  Dermatology  at  Jefferson  Medical  College.  Third 
Edition.  Revised  and  Enlarged.  With  Formulae  and  Illustrations,  several  being 
in  Colors.     580  pages.  Cloth,  $2.75 

"As  would  naturally  be  expected  from  the  author,  his  views  are  sound,  his  information 

extensive,  and  in  matters  of  practical  detail  the  hand  of  the  experienced  physician  is  everywhere 

visible."—  The  Medical  News. 

VIRCHOWS  Post-mortem  Examinations.  A  Description  and  Explanation  of  the 
Method  of  Performing  them  in  the  Dead-House  of  the  Berhn  Charite  Hospital, 
with  especial  reference  to  Medico-legal  Practice.  By  Prof.  Virchow.  Trans- 
lated by  Dr.  T.  P.  Smith.    Illustrated.    Third  Edition,  with  Additions.    Cloth,  .75 

VOSWINKEL.  Surgical  Nursing.  A  Manual  for  Nurses.  By  Bertha  M.  Vos- 
winkel.  Graduate  Episcopal  Hospital,  Philadelphia;  late  Nurse  in  Charge  Chil- 
dren's Hospital,  Columbus,  O.  Second  Edition,  Revised  and  Enlarged.  1 1 1  Illus- 
trations.   i2mo.  Cloth,  $1.00 

WALKER.  Students'  Aid  in  Ophthalmology.  By  Gertrude  A.  Walker, 
A.B.,  M.D.,  Clinical  Instructor  in  Diseases  of  the  Eye  at  Woman's  Medical 
College  of  Pennsylvania.   40  Illustrations  and  Colored  Plate.    i2mo.   Cloth,  $1.50 

WALSHAM.  Surgery  ;  its  Theory  and  Practice.  For  Students  and  Physicians. 
By  Wm.  J.  Walsham,  m.d.,  f.r.c.S.,  Senior  Ass't  Surg,  to,  and  Dem.  of  Practi- 
cal  Surg,  in,  St.  Bartholomew's  Hospital,  Surg,  to  Metropolitan  Free  Hospital, 
London?  Sixth  Edition,  Revised  and  Enlarged.  With  410  Engravings.  Clo.,^3.00 

WARD.  Notes  on  Massage;  Including  Elementary  Anatomy  and  Physiology. 
Bv  Jessie  M.  Ward,  Instructor  in  Massage  in  the  Pennsylvania,  Philadelphia, 
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etc.     i2mo.     Interleaved.  Paper  Cover,  $1.00 

WARING.  Practical  Therapeutics.  A  Manual  for  Physicians  and  Students.  By 
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Crown  Octavo.  Cloth,  $2.00 ;  Leather,  $3.00 

WARREN.  Compend  Dental  Pathology  and  Dental  Medicine.  Containing  all 
the  most  noteworthy  points  of  interest  to  the  Dental  Student  and  a  Chapter 
on  Emergencies.  By  Geo.  W.  Warren,  d.d.s..  Clinical  Chief,  Penn'a  College 
of  Dental  Surgery,  Phila.  Third  Edition,  Enlarged.  Illustrated.  Being  No. 
13  f  Quiz- Compend  f  Series.     i2mo.  Cloth,  .80 

Interleaved  for  the  addition  of  Notes,  $1.25 
Dental  Prosthesis  and  Metallurgy.     129  Illustrations.  Cloth,  $1.25 

WATSON  on  Amputations  of  the  Extremities  and  Their  Complications.  By 
B.  A.  Watson,  M.D.     250  Illustrations.  Cloth,  $5.50 

Concussions.     An  Experimental  Study  of  Lesions  arising  from  Severe  Con- 
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WELLS.  Compend  of  Gynecology.  By  Wm.  H.  Wells,  m.d..  Instructor  of 
Obstetrics,  Jefferson  Medical  College,  Philadelphia;  Fellow  of  the  College  of 
Physicians  of  Philadelphia.  Second  Edition,  Revised.  140  Illustrations. 
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MEDICAL  AND  SCIENTIFIC  PUBLICATIONS.  29 

WESTLAND.  The  Wife  and  Mother.  A  Handbook  for  Mothers.  By  A. 
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WETHERED.  Medical  Microscopy.  A  Guide  to  the  Use  of  the  Microscope  in 
Practical  Medicine.  By  Frank  J.  Wethered,  m.d  ,  m.r.c.p.,  Demonstrator  of 
Practical  Medicine,  Middlesex  Hospital  Medical  School;  Assistant  Physician, 
late  Pathologist,  City  of  London  Hospital  for  Diseases  of  Chest,  etc.  With  a 
Colored  Plate  and  loi  Illustrations.     406  Pages.     i2mo.  Cloth,  $2.00 

WEYL.  Sanitary  Relations  of  the  Coal-Tar  Colors.  By  Theodore  Weyl. 
Authorized  Translation  by  Henry  Leffmann,  m.d.,  ph.d.     i2mo.     154  pages. 

Cloth,  $1.25 

WHITACRE.  Laboratory  Text-Book  of  Pathology.  By  Horace  J.  Whitacre, 
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trated with  121  original  Illustrations.     8vo.  Cloth,  $1.50 

"WHITE.    The  Mouth  and  Teeth.    By  J.  W.  White,  m.d.,  d.d.s.  Cloth,  .40 

WHITE  AND  WILCOX.  Materia  Medica,  Pharmacy,  Pharmacology,  and 
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and  Hospital ;  Visiting  Physician  St.  Mark's  Hospital;  Assistant  Visiting  Physi- 
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Cloth,  $3.00;  Leather,  I3. 50 

WILLIAMS.  Manual  of  Bacteriology.  By  Herbert  U.  Williams,  m.d..  Pro- 
fessor of  Pathology  and  Bacteriology,  Medical  Department  University  of  Buffalo. 
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WILSON.  Handbook  of  Hygiene  and  Sanitary  Science.  By  George  Wilson, 
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With  Illustrations.     Eighth  Edition.    i2mo.  Cloth,  $3.00 

WILSON.  The  Summer  and  its  Diseases.  By  James  C.  Wilson,  m.d..  Prof,  of  the 
Practice  of  Med.  and  Clinical  Medicine,  Jefferson  Med.  Coll.,  Phila.     Cloth,  .40 

WILSON.  System  of  Human  Anatomy,  nth  Revised  Edition.  Edited  by  Henry 
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Glossary  of  Terms.     Thick  i2mo.  Cloth,  $5.00 

WINCKEL.  Text-Book  of  Obstetrics  ;  Including  the  Pathology  and  Therapeutics 
of  the  Puerperal  State.  By  Dr.  F.  Winckel,  Professor  of  Gynecology  and 
Director  of  the  Royal  University  Clinic  for  Women  in  Munich.  Authorized 
Translation  by  J.  Clifton  Edgar,  a.m.,  m.d..  Adjunct  Professor  to  the  Chair  of 
Obstetrics,  Medical  Department,  University  City  of  New  York.  With  nearly  200 
Handsome  Illustrations,  the  majority  of  which  are  original  with  this  work.  Octavo. 

Cloth,  $5.00;  Leather,  $6.00 

WINDLE.    Surface  Anatomy  and  Landmarks.    By  B.  C.  A.  Windle,  d.sc.m.d., 

Professor  of  Anatomy  in  Mason  College ,  Birmingham,  etc.  Second  Edition, 
Revised  by  T.  Manners  Smith,  m.r.c.s.,  with  Colored  and  other  Illustrations. 
i2mo.  Cloth,  $1.00 

WOAKES.     Deafness,   Giddiness,   and   Noises  in  the  Head.     By  Edward 

Woakes,  m.d..  Senior  Aural  Surgeon,  London  Hospital ;  assisted  by  Claud 
Woakes,  m.r.c.s.,  Assistant  Surgeon  to  the  London  Throat  Hospital.  Fourth 
Edition.     Illustrated.     i2mo.  Cloth,  $2.00 

WOOD.  Brain  Work  and  Overwork.  By  Prof.  H.  C.  Wood,  Chnical  Professor 
of  Nervous  Diseases,  University  of  Pennsylvania.     i2mo.  Cloth,  .40 

WOODY.  Essentials  of  Chemistry  and  Urinalysis.  By  Sam  E.  Woody,  a.m., 
M.D.,  Professor  of  Chemistry  and  Public  Hygiene,  and  Clinical  Lecturer  on 
Diseases  of  Children,  in  the  Kentucky  School  of  Medicine.  Fourth  Edition. 
Illustrated,     i2mo.  hi  Press. 


From  the  Southern  Clinic. 

"  'We  know  of  no  series  of  books  issued  by  any  house  that  so  fully  meets  our  approval  as  these 
.?  Quiz-Compends  ?.  They  are  well  arranged,  full,  and  concise,  and  are  really  the  best  line  of  text- 
books that  could  be  found  for  either  student  or  practitioner.' 

BLAKISTON'S  ?QUIZ=COMPENDS? 

The  Best  Series  of  Manuals  for  the  Use  of  Students. 

Price  of  each.  Cloth,  .80.         Interleaved  for  taking  Notes,  $1.25. 

These  Compends  are  based  on  the  most  popular  text-books  and  the  lectures  of  promi- 


nent professors,  and  are  kept  constantly  revised,  so  that  they  may  thoroughly  represent  the 
present  state  of  the  subjects  upon  which  they  treat.  The  authors  have  had  large  experience  as 
Quiz-Masters  and  attaches  of  colleges,  and  are  well  acquainted  with  the  wants  of  students.  They 
are  arranged  in  the  most  approved  form,  thorough  and  concise,  containing  over  600  fine  illustra- 
tions, inserted  wherever  they  could  be  used  to  advantage.  Can  be  used  by  students  of  any 
college,  and  contain  information  nowhere  else  collected  in  such  a  condensed,  practical  shape. 

ILLUSTRATED  CIRCULAR  FREE. 

No.  I.  HUMAN  ANATOMY.  Sixth  Revised  and  Enlarged  Edition.  Including  Vis- 
ceral Anatomy.  Can  be  used  with  either  Morris's  or  Gray's  Anatomy.  1 17  Illustrations 
and  16  Lithographic  Plates  of  Nerves  and  Arteries,  with  Explanatory  Tables,  etc.  By 
Samuel  O.  L.  Potter,  m.d.  ,  Professor  of  the  Practice  of  Medicine,  College  of  Physicians 
and  Surgeons,  San  Francisco;  late  A.  A.  Surgeon,  U.  S.  Army. 

No.  2.  PRACTICE  OF  MEDICINE.  Parti.  Sixth  Edition,  Revised,  Enlarged,  and 
Improved.  By  Dan'l  E.  Hughes,  m.d.,  Physician-in- Chief,  Philadelphia  Hospital,  late 
Demonstrator  of  Clinical  Medicine,  Jefferson  Medical  College,  Philadelphia. 

No.  3.     PRACTICE  OF  MEDICINE.    Part  II.    Sixth  Edition,  Revised,  Enlarged,  and 

Improved.      Same  author  as  No.  2. 

No.  4.  PHYSIOLOGY.  Ninth  Edition,  with  new  Illustrations  and  a  table  of  Physio- 
logical Constants.  Enlarged  and  Revised.  By  A.  P.  Bruba.ker,  m.d.,  Professor  of 
Physiology  and  General  Pathology  in  the  Pennsylvania  College  of  Dental  Surgery;  Demon- 
strator of  Physiology,  Jefferson  Medical  College,  Philadelphia. 

No.  5.  OBSTETRICS.  Sixth  Edition.  By  Henry  G.  Landis,  m.d.  Revised  and  Edited 
by  Wm.  H.  Wells,  m.d..  Instructor  of  Obstetrics,  Jefferson  Medical  College,  Philadelphia. 
Enlarged.     3  Plates  and  47  other  Illustrations. 

No.  6.  MATERIA  MEDICA,  THERAPEUTICS,  AND  PRESCRIPTION 
WRITING.  Sixth  Revised  Edition  (U.  S.  P.  1890).  By  Samuel  O.  L.  Potter,  m.d., 
Professor  of  the  Practice  of  Medicine,  College  of  Physicians  and  Surgeons,  San  Francisco. 

No.  7.  GYNECOLOGY.  Second  Edition.  By  Wm.  H.  Wells,  m.d.,  Instructor  of  Ob- 
stetrics, Jefferson  Medical  College,  Philadelphia.      140  Illustrations. 

No.  8.  DISEASES  OF  THE  EYE  AND  REFRACTION.  Second  Edition.  Includ- 
ing Treatment  and  Surgery  and  a  Section  on  Local  Therapeutics.  By  George  M.  Gould, 
m.d.,  and  W.  L.  Pyle,  m.d.  With  Formulas,  Glossary,  several  useful  Tables,  and  109 
Illustrations,  several  of  which  are  colored. 

No.  9.  SURGERY,  Minor  Surgery,  and  Bandaging.  Fifth  Edition,  Enlarged  and  Im- 
proved. By  Orville  Horwitz,  b.s.,  m.d.,  Clinical  Professor  of  Genito-Urinary  Surgery 
and  Venereal  Diseases  in  Jefferson  Medical  College  ;  Surgeon  to  Philadelphia  Hospital,  etc. 
With  98  Formulae  and  167  Illustrations. 

No.  10.  MEDICAL  CHEMISTRY.  Fourth  Edition.  Including  Urinalysis,  Animal 
Chemistry,  Chemistry  of  Milk,  Blood,  Tissues,  the  Secretions,  etc.  By  He.nry  Leffmann, 
m.d..  Professor  of  Chemistry  in  Pennsylvania  College  of  Dental  Surgery  and  in  the 
Woman's  Medical  College,  Philadelphia. 

No.  II.  PHARMACY.  Fifth  Edition.  Based  upon  Prof  Remington's  Text-Book  of  Phar- 
macy. By  F.  E.  Stewart,  m.d.,  ph.g.,  late  Quiz-Master  in  Pharmacy  and  Chemistry, 
Philadelphia  College  of  Pharmacy ;   Lecturer  at  Jefferson  Medical  College. 

No.  12.  VETERINARY  ANATOMY  AND  PHYSIOLOGY.  Illustrated.  By 
Wm.  R.  Ballou,  m.d..  Professor  of  Equine  Anatomy  at  New  York  College  of  Veterinary 
Surgeons  ;   Physician  to  Bellevue  Dispensary,  etc.     With  29  graphic  Illustrations. 

No.  13.  DENTAL  PATHOLOGY  AND  DENTAL  MEDICINE.  Third  Edition, 
Illustrated.  Containing  all  the  most  noteworthy  points  of  interest  to  the  Dental  Student  and 
a  Section  on  Emergencies.  By  Geo.  W.  Warren,  d.d.s.,  Chief  of  Clinical  Staff,  Pennsyl- 
vania College  of  Dental  Surgery,  Philadelphia. 

No.  14.  DISEASES  OF  CHILDREN.  Colored  Plate.  By  Marcus  P.  Hatfield, 
Professor  of  Diseases  of  Ciuldren,  Chicago  Medical  College.      Second  Edition,  Enlarged. 

No.  15.  GENERAL  PATHOLOGY  AND  MORBID  ANATOMY.  91  Illustra- 
tions. By  H.  Newberry  Hall,  ph.g.,  m.d..  Professor  of  Pathology  and  Medical  Chem- 
istry, Chicago  Post-Graduate  Medical  School.     Second  Edition. 

No.  16.  DISEASES  OF  THE  SKIN.  By  Jay  F.  Schamberg,  m.d..  Instructor  at 
Philadelphia  Polyclinic.     99  Illustrations. 

Price,  each,  strongfly  bound  in  cloth,  .80.    Interleaved  for  taking:  Notes,  $1.25. 


Published  Annually  for  49  Years. 

The  Physicians  Visiting  List. 

(LINDSAY  &  BLAKISTON'S.) 

Issued  in  November  of  each  Year. 


In  order  to  improve  and  simplify  this  Visiting  List  we  have  done  away  with  the  two 
styles  hitherto  known  as  the  "  25  and  50  Patients  plain."  We  have  allowed  more  space 
for  writing  the  names,  and  added  to  the  special  memoranda  page  a  column  for  the 
"Amount"  of  the  weekly  visits  and  a  column  for  the  "Ledger  Page."  To  do  this  with- 
out increasing  the  bulk  or  the  price,  we  have  condensed  the  reading  matter  in  the  front 
of  the  book  and  rearranged  and  simplified  the  memoranda  pages,  etc.,  at  the  back. 

The  Lists  for  75  Patients  and  100  Patients  will  also  have  special  memoranda  page  as 
above,  and  hereafter  will  come  in  two  volumes  only,  dated  January  to  June,  and  July  to 
December.  While  this  makes  a  book  better  suited  to  the  pocket,  the  chief  advantage  is 
that  it  does  away  with  the  risk  of  losing  the  accounts  of  a  whole  year  should  the  book 
be  mislaid. 

The  changes  and  improvements  made  in  1896  met  with  such  general 
favor  that  the  sale  increased  at  once  more  than  ten  per  cent,  over  the 
previous  year. 


CONTENTS. 


PRELIMINARY  MATTER.— Calendar,  1 900-1 901— Table  of  Signs,  to  be  used  in  keeping  records— 
The  Metric  or  French  Decimal  System  of  Weights  and  Measures — Table  for  Converting  Apothecaries' 
Weights  and  Measures  into  Grams — Dose  Table,  giving  the  doses  of  official  and  unofficial  drugs  in  both 
the  English  and  Metric  Systems — Asphyxia  and  Apnea — Complete  Table  for  Calculating  the  Period  of 
Utero- Gestation  —  Comparison  of  Thermometers. 

VISITING  LIST. — Ruled  and  dated  pages  for  25, 50, 75,  and  100  patients  per  day  or  week,  with  blank  page 
opposite  each  on  which  is  an  amount  column,  column  for  ledger  page,  and  space  for  special  memoranda. 

SPECIAL  RECORDS  for  Obstetric  Engagements,  Deaths,  Births,  etc.,  with  special  pages  for  Addresses 
of  Patients,  Nurses,  etc..  Accounts  Due,  Cash  Account,  and  General  Memoranda. 


SIZES  AND    PRICES. 

REGULAR  EDITION,  as  Described  Above. 

BOUND   IN   STRONG   LEATHER   COVERS,  WITH    POCKET  AND    PENCIL. 

For  25  Patients  weekly,  with  Special  Memoranda  Page, $100 

50        "  "  "  "  "         I   25 

CO  u  »  u  u  u  2  vols    /  Ja""a''y    to    Ju"e      I  2    00 

•'  '  \  July  to  December  j      •■•••• 

71;    «      «        "  «        "    2  vols  /  J^^'^^'y  *°  J""^  1  200 

■^  'I  July  to  December  / 

100  "  «  «  «  "  2V0ls.ijT!"^A°    ^T      \ 2    25 

[  July  to  December  J  -^ 

PERPETUAL  EDITION,  without  Dates. 

No.  I.  Containing  space  for  over  1300  names,  with  blank  page  opposite  each  Visiting  List  page. 

Bound  in  Red  Leather  cover,  with  Pocket  and  Pencil, $1   25 

No.  2.  Same  as  No.  i.     Containing  space  for  2600  names,  with  blank  page  opposite, i  5° 

MONTHLY  EDITION,  without  Dates. 

No.  I.  Bound,  Seal  leather,  without  Flap  or  Pencil,  gilt  edges, 75 

No.  2.  Bound,  Seal  leather,  with  Tucks,  Pencil,  etc.,  gilt  edges, I  00 

S^°  All  these  prices  are  net.     No  discount  can  be  allowed  retail  purchasers. 
Circular  and  sample  pages  upon  application. 


MORRIS' 


Text=Book  of  Anatomy 

SECOND  EDITION 
Thoroughly  Revised  and  Greatly  Improved 

790  Illustrations,  of  which  many  are  in  Colors 

Royal  Octavo.    Cloth,  $6.00 ;  Sheep,  $7.00 ;  Half  Russia,  $8.00 


Two  Reviews   Recently  Published 
by  Two  Leading  Medical  Journals 


From 

The  Medical  Record,  New  York. 

"  The  reproach  that  the  English  lan- 
guage can  boast  of  no  treatise  on  anatomy- 
deserving  to  be  ranked  with  the  masterly 
works  of  Henle,  Luschka,  Hyrtl,  and 
others,  is  fast  losing  its  force.  During 
the  past  few  years  several  works  of  great 
merit  have  appeared,  and  among  these 
Morris's  "  Anatomy  "  seems  destined  to 
take  the  first  place  in  disputing  the  palm 
in  anatomical  fields  with  the  German 
classics.  The  nomenclature,  arrange- 
ment, and  entire  general  character  re- 
semble strongly  those  of  the  above-men- 
tioned handbooks,  while  in  the  beauty 
and  profuseness  of  its  illustrations  it  sur- 
passes them.  This  edition  ofters  but  few 
changes  ;  a  chapter  on  the  skin  has  been 
added,  and  a  useful  list  of  vestigial  and 
abnormal  structures  has  been  compiled. 
Sections  especially  worthy  of  praise  are 
those  on  surgical  and  topographical  anat- 
omy, and  the  chapter  on  the  nervous 
system  is  presented  with  great  clearness 
and  fullness.  The  ever-growing  popu- 
larity of  the  book  with  teachers  and 
students  is  an  index  of  its  value,  and  it 
may  safely  be  recommended  to  all  inter- 
ested." 


From 

The  Philadelphia  Medical  Journal. 

"  Of  all  the  text-books  of  moderate  size 
on  human  anatomy  in  the  English  lan- 
guage, Morris  is  undoubtedly  the  most 
up-to-date  and  accurate.  The  changes 
from  the  first  edition  are  not  marked ; 
perhaps  the  most  noticeable  feature  is 
that  there  are  twenty  less  cuts  than  in  the 
first  edition.  Those  which  have  been 
omitted,  however,  will  not  be  greatly 
missed.  The  saving  of  space  by  the 
omission  of  a  discussion  of  histology  is  a 
decided  advantage,  giving  room  for  much 
matter  of  importance  in  these  days  when 
every  student  is  obliged  to  own  a  special 
treatise  on  histology.  To  enumerate  the 
numerous  differences  which  are  notice- 
able in  the  descriptions  given  by  this  book 
from  those  in  many  of  the  older  anatomies 
would  require  too  much  space.  The 
changes,  however,  almost  without  excep- 
tion, tend  toward  an  improved  nomen- 
clature and  greater  accuracy.  This  is 
particularly  noticeable  in  the  parts  de- 
voted to  descriptions  of  the  abdominal 
viscera  and  the  joints.  .  .  .  For  the  stu- 
dent, the  surgeon,  or  for  the  general  prac- 
titioner who  desires  to  review  hisanatomy, 
Morris  is  decidedly  the  book  to  buv." 


\*The  illustrations  in  number,  correctness,  and  excellence  of  execution 
are  equaled  by  no  similar  treatise,  about  $1000  having  been  expended  on 
new  and  improved  blocks  for  this  edition  alone.     Handsome  circular  free. 


COLUMBIA  UNIVERSITY  LIBRARIES 

This  book  is  due  on  the  date  indicated  below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing:, 
as  provided  by  the  library  rules  or  by  special  arrangement 
with  the  Librarian  in  charge. 

DATE  BORROWED 

DATE  DUE 

DATE  BORROWED 

DATE  DUE 

C23    (1264)    BOM 

RC660 

^^^"  1900 

<^  diabetes  mp-n-;  +  , 
suria,       "^^ilitus  and  gi^^co- 


(S'oo 


